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    Clinical Trial Results:
    A Phase III Randomized, Placebo-Controlled Clinical Trial to Assess the Safety and Efficacy of Odanacatib (MK-0822) to Reduce the Risk of Fracture in Osteoporotic Postmenopausal Women Treated With Vitamin D and Calcium (MK-0822-018)

    Summary
    EudraCT number
    		 2007-002693-66
    Trial protocol
    		 LT   DK   CZ   PL   GB   DE   FR   BE   LV   EE   IT   ES   BG  
    Global end of trial date
    01 Feb 2017

    Results information
    Results version number
    		 v1
    This version publication date
    03 Mar 2018
    First version publication date
    03 Mar 2018
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    0822-018
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00529373
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Secondary Id: 2007_610, Registry Identifier: 132238
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Feb 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Feb 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of the event-driven base study is to determine the safety and efficacy, especially fracture risk reduction, of odanacatib in postmenopausal women diagnosed with osteoporosis. In a placebo-controlled extension of the base study, participants continued to receive the same blinded study medication for a total of up to 5 years of blinded study medication combined between the base study and the extension. After participants received 5 years of blinded study medication, they received open-label odanacatib through the end of the first extension. Participants were then invited to enroll in a second extension study in which they received open-label odanacatib for an additional 5 years. Two imaging substudies (PN032-Base/Extension and PN035) were conducted for participants in the MK-0822-018 Study. Additional safety information was collected for participants who discontinued from the base study or the blinded first extension in an observational follow-up study, MK-0822-083.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 Participants received standard-of-care therapy with Vitamin D3 (oral tablet; 5600 IU orally once weekly [OW]) and calcium carbonate (oral tablet; total daily calcium intake approximately 1200 mg but not to exceed 1600 mg) dietary supplements.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Sep 2007
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy, Regulatory reason
    Long term follow-up duration
    		 10 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 280
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Belgium: 37
    Country: Number of subjects enrolled
    Brazil: 1611
    Country: Number of subjects enrolled
    Bulgaria: 220
    Country: Number of subjects enrolled
    Chile: 62
    Country: Number of subjects enrolled
    China: 610
    Country: Number of subjects enrolled
    Colombia: 1999
    Country: Number of subjects enrolled
    Croatia: 33
    Country: Number of subjects enrolled
    Czech Republic: 317
    Country: Number of subjects enrolled
    Denmark: 1048
    Country: Number of subjects enrolled
    Dominican Republic: 144
    Country: Number of subjects enrolled
    Estonia: 170
    Country: Number of subjects enrolled
    France: 42
    Country: Number of subjects enrolled
    Germany: 27
    Country: Number of subjects enrolled
    Guatemala: 293
    Country: Number of subjects enrolled
    Hong Kong: 211
    Country: Number of subjects enrolled
    India: 981
    Country: Number of subjects enrolled
    Italy: 79
    Country: Number of subjects enrolled
    Japan: 454
    Country: Number of subjects enrolled
    Korea, Republic of: 194
    Country: Number of subjects enrolled
    Latvia: 53
    Country: Number of subjects enrolled
    Lebanon: 19
    Country: Number of subjects enrolled
    Lithuania: 178
    Country: Number of subjects enrolled
    Mexico: 421
    Country: Number of subjects enrolled
    New Zealand: 86
    Country: Number of subjects enrolled
    Norway: 289
    Country: Number of subjects enrolled
    Peru: 603
    Country: Number of subjects enrolled
    Philippines: 116
    Country: Number of subjects enrolled
    Poland: 1171
    Country: Number of subjects enrolled
    Romania: 129
    Country: Number of subjects enrolled
    Russian Federation: 793
    Country: Number of subjects enrolled
    Serbia: 60
    Country: Number of subjects enrolled
    South Africa: 1129
    Country: Number of subjects enrolled
    Spain: 61
    Country: Number of subjects enrolled
    Switzerland: 27
    Country: Number of subjects enrolled
    Taiwan: 64
    Country: Number of subjects enrolled
    Ukraine: 84
    Country: Number of subjects enrolled
    United Kingdom: 1711
    Country: Number of subjects enrolled
    United States: 262
    Worldwide total number of subjects
    16071
    EEA total number of subjects
    5565
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    12
    From 65 to 84 years
    15650
    85 years and over
    409

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Additional screening criteria applied.

    Period 1
    Period 1 title
    Base Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Odanacatib 50 mg OW
    Arm description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Arm title
    		 Placebo
    Arm description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo for Odanacatib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Number of subjects in period 1
    		Odanacatib 50 mg OW Placebo
    Started
    8043
    8028
    Completed
    6092
    6198
    Not completed
    1951
    1830
         Adverse event, serious fatal
    269
    241
         Physician decision
    60
    52
         Consent withdrawn by subject
    1062
    967
         Adverse event, non-fatal
    256
    229
         Other Protocol Specified Criteria
    19
    20
         Lost to follow-up
    221
    208
         Lack of efficacy
    16
    75
         Protocol deviation
    48
    38
    Period 2
    Period 2 title
    Transition to First Extension Study
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Odanacatib 50 mg OW
    Arm description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Arm title
    		 Placebo
    Arm description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo for Odanacatib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Number of subjects in period 2
    		Odanacatib 50 mg OW Placebo
    Started
    6092
    6198
    Completed
    4297
    3960
    Not completed
    1795
    2238
         Did not continue into first extension
    1795
    2238
    Period 3
    Period 3 title
    First Extension Double Blind Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Odanacatib 50 mg OW
    Arm description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Arm title
    		 Placebo
    Arm description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo for Odanacatib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Number of subjects in period 3
    		Odanacatib 50 mg OW Placebo
    Started
    4297
    3960
    Completed
    3640
    2961
    Not completed
    657
    999
         Adverse event, serious fatal
    109
    86
         Physician decision
    50
    45
         Consent withdrawn by subject
    296
    287
         Adverse event, non-fatal
    53
    56
         Missing disposition
    -
    1
         Other Protocol Specified Criteria
    27
    47
         Lost to follow-up
    41
    37
         Lack of efficacy
    65
    427
         Protocol deviation
    16
    13
    Period 4
    Period 4 title
    First Extension Open Label Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Odanacatib 50 mg OW
    Arm description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Arm title
    		 Odanacatib 50 mg OW (originally assigned to Placebo)
    Arm description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Number of subjects in period 4
    		Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Started
    3640
    2961
    Completed
    3432
    2615
    Not completed
    208
    346
         Adverse event, serious fatal
    36
    20
         Physician decision
    11
    9
         Consent withdrawn by subject
    71
    49
         Adverse event, non-fatal
    19
    17
         Missing disposition
    2
    5
         Other Protocol Specified Criteria
    20
    14
         Lost to follow-up
    11
    22
         Lack of efficacy
    36
    205
         Protocol deviation
    2
    5
    Period 5
    Period 5 title
    Transition to Second Extension
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Odanacatib 50 mg OW
    Arm description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Arm title
    		 Odanacatib 50 mg OW (originally assigned to Placebo)
    Arm description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Number of subjects in period 5
    		Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Started
    3432
    2615
    Completed
    3144
    2309
    Not completed
    288
    306
         Did not continue into second extension
    288
    306
    Period 6
    Period 6 title
    Second Extension Study
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Odanacatib 50 mg OW
    Arm description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Arm title
    		 Odanacatib 50 mg OW (originally assigned to Placebo)
    Arm description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odanacatib
    Investigational medicinal product code
    Other name
    MK-0822
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablet orally OW

    Number of subjects in period 6
    		Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Started
    3144
    2309
    Completed
    2844
    2112
    Not completed
    300
    197
         Adverse event, serious fatal
    86
    39
         Physician decision
    63
    26
         Consent withdrawn by subject
    97
    75
         Adverse event, non-fatal
    15
    12
         Missing disposition
    5
    5
         Other Protocol Specified Criteria
    7
    12
         Lost to follow-up
    18
    12
         Lack of efficacy
    7
    15
         Protocol deviation
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group values
    		 Odanacatib 50 mg OW Placebo Total
    Number of subjects
    		 8043 8028 16071
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 6 6 12
        From 65-84 years
    		 7826 7824 15650
        85 years and over
    		 211 198 409
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.8 ( 5.4 ) 72.9 ( 5.3 ) -
    Sex: Female, Male
    sxsss
    Units: Subjects
        Female
    		 8043 8028 16071
        Male
    		 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 97 88 185
        Asian
    		 1421 1411 2832
        Native Hawaiian or Other Pacific Islander
    		 1 1 2
        Black or African American
    		 129 132 261
        White
    		 4528 4557 9085
        More than one race
    		 1867 1839 3706
        Unknown or Not Reported
    		 0 0 0
    Stratum
    Units: Subjects
        Prior Vertebral Fracture|
    		 3733 3737 7470
        No Prior Vertebral Fracture|
    		 4310 4291 8601
    Bisphosphonate-Intolerant
    Units: Subjects
        Yes-
    		 1423 1447 2870
        No-
    		 6615 6574 13189
        Data N/A
    		 5 7 12

    End points

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    End points reporting groups
    Reporting group title
    Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Reporting group title
    Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Reporting group title
    Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Reporting group title
    Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Odanacatib 50 mg OW (originally assigned to Placebo)
    Reporting group description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Reporting group title
    Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Odanacatib 50 mg OW (originally assigned to Placebo)
    Reporting group description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Reporting group title
    Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Odanacatib 50 mg OW (originally assigned to Placebo)
    Reporting group description
    		 Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Primary: Base Study: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture

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    End point title
    		 Base Study: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    End point description
    Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures occurring after baseline were confirmed by quantitative morphometric (QM) and either SQ or binary SQ methodologies. A time-to-event methodology was used: life-table estimates of the proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and at yearly intervals; an interval-censored approach was used to determine incidence rate (number of participants with a morphometric fracture per 100 patient-years of follow-up). The Full-Analysis-Set (FAS) including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) with at least one spine radiograph on treatment (and at baseline) was used for analysis.
    End point type
    Primary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6770
    6910
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    1.27
    2.74
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    Generalized linear model for binary data with cloglog link and terms for time interval, treatment, stratum, and geographic region. cloglog link = complementary log log transformation of probability of an event up to the time-point.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13680
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Generalized linear model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 0.53

    Primary: Base Study: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)

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    End point title
    		 Base Study: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
    End point description
    Osteoporotic clinical hip fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.
    End point type
    Primary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    0.28
    0.54
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    The Cox proportional hazards model included terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 0.71

    Primary: Base Study: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)

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    End point title
    		 Base Study: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
    End point description
    Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excl. fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anat. sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (# of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all rand. participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.
    End point type
    Primary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    1.85
    2.41
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    The Cox proportional hazards model included terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.87

    Primary: Base Study + First Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture

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    End point title
    		 Base Study + First Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    End point description
    Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures occurring after baseline were confirmed by quantitative morphometric (QM) and either SQ or binary SQ methodologies. A time-to-event methodology was used: life-table estimates of the proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and at yearly intervals; an interval-censored approach was used to determine incidence rate (number of participants with a morphometric fracture per 100 patient-years of follow-up). The Full-Analysis-Set (FAS) including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) with at least one spine radiograph on treatment (and at baseline) was used for analysis.
    End point type
    Primary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6909
    7011
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    1.33
    2.74
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    Generalized linear model for binary data with cloglog link and terms for time interval, treatment, stratum, and geographic region. cloglog link = complementary log log transformation of probability of an event up to the time-point.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13920
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Generalized linear model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.55

    Primary: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)

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    End point title
    		 Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
    End point description
    Osteoporotic clinical hip fractures was confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided.
    End point type
    Primary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    0.29
    0.56
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    The Cox proportional hazards model included terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 0.67

    Primary: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)

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    End point title
    		 Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
    End point description
    Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur and shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided.
    End point type
    Primary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    1.78
    2.41
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    The Cox proportional hazards model included terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.83

    Primary: Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip

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    End point title
    		 Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip [1]
    End point description
    BMD was measured by dual-energy x-ray absorptiometry (DXA) at the total hip starting at screening & at yearly intervals until the end of study (second ext. study) for all participants who entered the second ext. study. Least squares (LS) means percent change in BMD from orig. baseline are provided through Month 108 (Year 9). At Months 96 (Year 8) & 108 (Year 9), approx. 3% or fewer patients in each treatment group had BMD data, & results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medic. in the base study. The FAS population incl. all rand. patients who took at least one dose of study medication & with necessary on-treatment info. (total hip BMD) was used for analysis (base study + first ext-dbp + second ext).
    End point type
    Primary
    End point timeframe
    Baseline and once yearly up to 10 years
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No between-group statistical comparisons were performed for this endpoint.
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    2997
    2212
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=2997, 2212)|
    3.03 (2.91 to 3.14)
    1.08 (0.95 to 1.22)
        Month 24 (n=2965, 2189)|
    4.32 (4.18 to 4.46)
    0.58 (0.42 to 0.74)
        Month 36 (n=2950, 2171)|
    5.60 (5.43 to 5.77)
    0.04 (-0.16 to 0.24)
        Month 48 (n=2905, 2133)|
    6.56 (6.36 to 6.76)
    -0.74 (-0.97 to -0.51)
        Month 60 (n=2718, 2015)|
    7.45 (7.22 to 7.68)
    -1.40 (-1.67 to -1.13)
        Month 72 (n=2186, 1637)|
    7.88 (7.62 to 8.14)
    -0.01 (-0.31 to 0.30)
        Month 84 (n=1631, 1197)|
    7.94 (7.63 to 8.26)
    0.97 (0.61 to 1.34)
        Month 96 (n=237, 187)|
    7.87 (7.38 to 8.37)
    1.57 (1.01 to 2.13)
        Month 108 (n=63, 51)|
    7.03 (6.02 to 8.05)
    1.11 (-0.02 to 2.23)
    No statistical analyses for this end point

    Primary: Imaging Substudy PN032-Base: Percent Change From Baseline in Volumetric Bone Mineral Density (vBMD) at the Lumbar Spine Using Quantitative Computed Tomography

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in Volumetric Bone Mineral Density (vBMD) at the Lumbar Spine Using Quantitative Computed Tomography
    End point description
    Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 24 (base study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine vBMD) was used for analysis (PN032-Base).
    End point type
    Primary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    46
    48
    Units: mg/cm^3
        least squares mean (confidence interval 95%)
    8.05 (4.48 to 11.62)
    -0.87 (-4.37 to 2.64)
    Statistical analysis title
    		 Odanacatib 50 mg vs Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.9
         upper limit
    		 13.93

    Primary: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in vBMD at the Lumbar Spine Using Quantitative Computed Tomography

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    End point title
    		 Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in vBMD at the Lumbar Spine Using Quantitative Computed Tomography
    End point description
    Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine vBMD) was used for analysis (PN032-Base + Extension).
    End point type
    Primary
    End point timeframe
    Baseline, Month 60
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    28
    25
    Units: mg/cm^3
        least squares mean (confidence interval 95%)
    14.76 (7.68 to 21.83)
    -11.69 (-18.69 to -4.69)
    Statistical analysis title
    		 Odanacatib 50 mg vs Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    26.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 16.49
         upper limit
    		 36.4

    Primary: Sarcopenia Substudy PN035: Change from Baseline in Appendicular Lean Body Mass (aLBM)

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    End point title
    		 Sarcopenia Substudy PN035: Change from Baseline in Appendicular Lean Body Mass (aLBM)
    End point description
    Sarcopenia is the age-related loss of skeletal muscle mass and associated loss of strength. Progression of sarcopenia was assessed using aLBM as measured by total body DXA. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS for change from baseline at specific time-points including all randomized particpants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (aLBM) was used for analysis (PN035).
    End point type
    Primary
    End point timeframe
    Baseline and once yearly up to 4 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    247
    257
    Units: kg
    least squares mean (confidence interval 95%)
        Month 12 (n=247, 257)|
    -0.20 (-0.28 to -0.12)
    -0.18 (-0.26 to -0.10)
        Month 24 (n=239, 236)|
    -0.19 (-0.28 to -0.10)
    -0.19 (-0.28 to -0.10)
        Month 36 (n=201, 187)|
    -0.36 (-0.45 to -0.27)
    -0.32 (-0.41 to -0.23)
        Month 48 (n=36, 32)|
    -0.44 (-0.64 to -0.24)
    -0.23 (-0.44 to -0.02)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.09
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.12
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.17
         upper limit
    		 0.09
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.08

    Primary: Sarcopenia Substudy PN035: Change from Baseline in Short Physical Performance Battery (SPPB) Score

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    End point title
    		 Sarcopenia Substudy PN035: Change from Baseline in Short Physical Performance Battery (SPPB) Score
    End point description
    The SPPB is used to assess physical function in older persons. The SPPB consists of 3 types of physical activities: standing balance, gait speed, and chair rise. Component activities are timed and then reduced to a categorical 0 to 4 scale based on time achieved. A higher composite score (range 0 to 12) indicates an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS for change from baseline at specific time-points including all randomized particpants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (SPPB) was used for analysis (PN035).
    End point type
    Primary
    End point timeframe
    Baseline and once yearly up to 4 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    251
    253
    Units: Score on a scale
    least squares mean (confidence interval 95%)
        Month 12 (n=251, 253)|
    0.03 (-0.16 to 0.22)
    -0.08 (-0.27 to 0.11)
        Month 24 (n=248, 235)|
    -0.04 (-0.25 to 0.16)
    -0.19 (-0.40 to 0.02)
        Month 36 (n=230, 221)|
    -0.18 (-0.42 to 0.06)
    -0.37 (-0.62 to -0.13)
        Month 48 (n=136, 111)|
    -0.05 (-0.34 to 0.24)
    -0.24 (-0.55 to 0.07)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.38
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.44
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.54
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.54

    Primary: Sarcopenia Substudy PN035: Percent Change from Baseline in Gait Speed

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    End point title
    		 Sarcopenia Substudy PN035: Percent Change from Baseline in Gait Speed
    End point description
    Gait speed is a component of the SPPB. Participants are asked to walk a distance of 4 meters at their normal pace. The test is performed 2 times, and the walk done in the shortest time is used for scoring. The activity is timed and then reduced to a categorical 0 to 4 scale based on time achieved. Higher scores indicate an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS for change from baseline at specific time-points including all randomized particpants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (gait speed) was used for analysis (PN035).
    End point type
    Primary
    End point timeframe
    Baseline and once yearly up to 4 years.
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    249
    252
    Units: Score on a scale
    least squares mean (confidence interval 95%)
        Month 12 (n=249, 252)|
    -0.02 (-0.10 to 0.06)
    -0.06 (-0.14 to 0.02)
        Month 24 (n=245, 233)|
    -0.02 (-0.11 to 0.07)
    -0.10 (-0.19 to -0.00)
        Month 36 (n=227, 218)|
    -0.09 (-0.19 to 0.02)
    -0.11 (-0.22 to -0.01)
        Month 48 (n=135, 111)|
    -0.15 (-0.28 to -0.02)
    -0.24 (-0.38 to -0.10)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    501
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.08
         upper limit
    		 0.15
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    501
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.21
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    501
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.17
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    501
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.28

    Primary: Base study: Rate of Adverse Events

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    End point title
    		 Base study: Rate of Adverse Events
    End point description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    100.16 (97.81 to 102.6)
    98.65 (96.33 to 101.01)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Miettinen & Nurminen method based 95% confidence interval
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in rates
    Point estimate
    1.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 4.84

    Primary: Base Study: Rate of Discontinuation from Study Treatment Due to an AE

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    End point title
    		 Base Study: Rate of Discontinuation from Study Treatment Due to an AE
    End point description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    2.97 (2.75 to 3.20)
    2.70 (2.49 to 2.92)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Miettinen & Nurminen method based 95% confidence interval
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in rates
    Point estimate
    0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.04
         upper limit
    		 0.58

    Primary: Base Study: Time to First 3-Point Major Adverse Cardiac Event (MACE) Confirmed by Thrombolysis in Myocardial Infarction Study Group (TIMI) Adjudication

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    End point title
    		 Base Study: Time to First 3-Point Major Adverse Cardiac Event (MACE) Confirmed by Thrombolysis in Myocardial Infarction Study Group (TIMI) Adjudication
    End point description
    The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    1.17
    1.04
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.182
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.34

    Primary: Base Study: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.48
    0.41
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.235
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.55

    Primary: Base study + First Extension: Rate of Adverse Events

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    End point title
    		 Base study + First Extension: Rate of Adverse Events
    End point description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    97.25 (95.00 to 99.53)
    96.36 (94.13 to 98.63)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Miettinen & Nurminen method based 95% Confidence Interval
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in rates
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 4.07

    Primary: Base Study + First Extension: Rate of Discontinuation from Study Treatment Due to an AE

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    End point title
    		 Base Study + First Extension: Rate of Discontinuation from Study Treatment Due to an AE
    End point description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    2.66 (2.48 to 2.86)
    2.55 (2.37 to 2.75)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Miettinen & Nurminen method based 95% Confidence Interval
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in rates
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.37

    Primary: Base Study + First Extension: Time to First 3-Point MACE Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First 3-Point MACE Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    1.24
    1.06
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.029
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.36

    Primary: Base Study + First Extension: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Primary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.51
    0.43
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.178
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.46

    Primary: Second Extension: Number of Participants who Experienced an Adverse Event

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    End point title
    		 Second Extension: Number of Participants who Experienced an Adverse Event [2]
    End point description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All-Participants-as-Treated population including all patients who took at least one dose of study medication was used for analysis (second extension study).
    End point type
    Primary
    End point timeframe
    Up to 5 years (in the second extension)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No between-group statistical comparisons were performed for this endpoint.
    End point values
    		 Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Number of subjects analysed
    3144
    2309
    Units: Participants
    2173
    1587
    No statistical analyses for this end point

    Primary: Second Extension: Number of Participants Discontinuing Study Treatment Due to an AE

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    End point title
    		 Second Extension: Number of Participants Discontinuing Study Treatment Due to an AE [3]
    End point description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All-Participants-as-Treated population including all patients who took at least one dose of study medication was used for analysis (second extension).
    End point type
    Primary
    End point timeframe
    Up to 5 years (in the second extension)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No between-group statistical comparisons were performed for this endpoint.
    End point values
    		 Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Number of subjects analysed
    3144
    2309
    Units: Participants
    55
    36
    No statistical analyses for this end point

    Secondary: Base Study: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)

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    End point title
    		 Base Study: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
    End point description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    0.16
    0.58
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    The Cox proportional hazards model included terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 0.4

    Secondary: Base Study: Yearly Rate of Height Loss

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    End point title
    		 Base Study: Yearly Rate of Height Loss
    End point description
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (height) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6112
    6231
    Units: cm/year
        least squares mean (confidence interval 95%)
    -0.13 (-0.14 to -0.12)
    -0.15 (-0.16 to -0.14)
    Statistical analysis title
    		 Odanacatib 50 mg OW versus Placebo.
    Statistical analysis description
    The mixed model contained fixed effects for treatment, region, stratum, treatment-year interaction and random effect intercept and slope (year) and unstructured covariance matrix.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12343
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.041
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.03

    Secondary: Base Study: Number of Participants with Height Loss of > 1 cm

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    End point title
    		 Base Study: Number of Participants with Height Loss of > 1 cm
    End point description
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (height loss) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6095
    6215
    Units: Participants
        Up to Month 12 (n=6095, 6215)|
    316
    365
        Up to Month 24 (n=5347, 5396)|
    592
    669
        Up to Month 36 (n=4745, 4632)|
    875
    944
        Up to Month 48 (n=331, 281)|
    90
    59
        Up to Month 60 (n=103, 70)|
    23
    12
        Overall/At any time (n=6095, 6215)|
    1022
    1149
    Statistical analysis title
    		 Odanacatib 50 mg OW versus Placebo.
    Statistical analysis description
    Treatment comparison for height loss at any time during the treatment period. The logistic model contained terms for treatment, geographic region and stratum.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12310
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.014
    Method
    		 Logistic model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 0.98

    Secondary: Base Study: Percent Change from Baseline in BMD Measurements of the Total Hip

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    End point title
    		 Base Study: Percent Change from Baseline in BMD Measurements of the Total Hip
    End point description
    BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6490
    6596
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=292, 302)|
    1.85 (1.54 to 2.16)
    0.53 (0.24 to 0.81)
        Month 12 (n=6490, 6596)|
    2.82 (2.74 to 2.91)
    0.33 (0.25 to 0.42)
        Month 24 (n=5916, 5895)|
    3.79 (3.68 to 3.90)
    -0.68 (-0.79 to -0.57)
        Month 36 (n=5127, 4925)|
    4.81 (4.67 to 4.94)
    -1.64 (-1.78 to -1.50)
        Month 48 (n=539, 452)|
    5.39 (5.04 to 5.74)
    -3.23 (-3.59 to -2.87)
        Month 60 (n=167, 138)|
    5.67 (5.13 to 6.21)
    -3.82 (-4.40 to -3.24)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.75
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.37
         upper limit
    		 2.61
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.31
         upper limit
    		 4.62
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.25
         upper limit
    		 6.64
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.11
         upper limit
    		 9.12
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.7
         upper limit
    		 10.29

    Secondary: Base Study: Percent Change from Baseline in BMD Measurements of the Lumbar Spine

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    End point title
    		 Base Study: Percent Change from Baseline in BMD Measurements of the Lumbar Spine
    End point description
    BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (lumbar spine BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6344
    6400
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=293, 299)|
    3.75 (3.39 to 4.11)
    0.78 (0.44 to 1.13)
        Month 12 (n=6344, 6400)|
    4.67 (4.56 to 4.77)
    0.59 (0.49 to 0.70)
        Month 24 (n=5805, 5778)|
    6.77 (6.64 to 6.90)
    0.72 (0.59 to 0.84)
        Month 36 (n=5086, 4913)|
    8.59 (8.43 to 8.74)
    0.75 (0.59 to 0.90)
        Month 48 (n=503, 441)|
    10.47 (10.09 to 10.86)
    0.76 (0.35 to 1.16)
        Month 60 (n=169, 138)|
    11.49 (10.82 to 12.17)
    0.26 (-0.47 to 1.00)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12744
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.47
         upper limit
    		 3.46
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12744
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.93
         upper limit
    		 4.22
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12744
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.87
         upper limit
    		 6.23
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12744
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    7.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.62
         upper limit
    		 8.06
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12744
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.16
         upper limit
    		 10.27
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12744
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    11.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.23
         upper limit
    		 12.23

    Secondary: Base Study: Percent Change from Baseline in BMD Measurements of the Femoral Neck

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    End point title
    		 Base Study: Percent Change from Baseline in BMD Measurements of the Femoral Neck
    End point description
    BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6490
    6597
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=292, 302)
    2.17 (1.78 to 2.55)
    0.68 (0.30 to 1.06)
        Month 12 (n=6490, 6597)
    2.80 (2.68 to 2.91)
    0.59 (0.48 to 0.70)
        Month 24 (n=5916, 5895)
    4.01 (3.88 to 4.15)
    -0.37 (-0.50 to -0.23)
        Month 36 (n=5126, 4925)
    5.45 (5.29 to 5.61)
    -1.01 (-1.17 to -0.85)
        Month 48 (n=539, 452)
    6.15 (5.74 to 6.56)
    -2.27 (-2.71 to -1.83)
        Month 60 (n=167, 138)
    6.69 (6.02 to 7.36)
    -1.84 (-2.58 to -1.11)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13087
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 2.03
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13087
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.05
         upper limit
    		 2.37
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13087
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.19
         upper limit
    		 4.57
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13087
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.24
         upper limit
    		 6.68
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13087
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.82
         upper limit
    		 9.02
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13087
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.54
         upper limit
    		 9.53

    Secondary: Base Study: Percent Change from Baseline in BMD Measurements of the Trochanter

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    End point title
    		 Base Study: Percent Change from Baseline in BMD Measurements of the Trochanter
    End point description
    BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6490
    6596
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=292, 302)
    2.65 (2.12 to 3.18)
    0.91 (0.43 to 1.38)
        Month 12 (n=6490, 6596)
    4.32 (4.18 to 4.46)
    0.82 (0.68 to 0.96)
        Month 24 (n=5916, 5895)
    6.17 (6.00 to 6.34)
    -0.24 (-0.41 to -0.07)
        Month 36 (n=5127, 4925)
    8.01 (7.81 to 8.22)
    -1.26 (-1.47 to -1.05)
        Month 48 (n=539, 452)
    9.46 (8.92 to 10.00)
    -2.98 (-3.54 to -2.42)
        Month 60 (n=167, 138)
    10.16 (9.32 to 10.99)
    -3.65 (-4.55 to -2.75)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 2.46
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.31
         upper limit
    		 3.7
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.17
         upper limit
    		 6.65
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.98
         upper limit
    		 9.57
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    12.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.66
         upper limit
    		 13.22
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13086
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    13.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.58
         upper limit
    		 15.04

    Secondary: Base Study: Percent Change from Baseline in BMD Measurements of the Distal-Third Forearm

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    End point title
    		 Base Study: Percent Change from Baseline in BMD Measurements of the Distal-Third Forearm
    End point description
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of participants at selected sites. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    679
    718
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=679, 718)
    0.51 (0.19 to 0.82)
    -0.60 (-0.91 to -0.30)
        Month 24 (n=619, 635)
    0.33 (-0.03 to 0.68)
    -1.02 (-1.37 to -0.68)
        Month 36 (n=569, 558)
    0.02 (-0.36 to 0.41)
    -1.90 (-2.29 to -1.52)
        Month 48 (n=85, 77)
    -0.62 (-1.52 to 0.28)
    -2.82 (-3.76 to -1.88)
        Month 60 (n=32, 26)
    0.29 (-1.08 to 1.66)
    -3.21 (-4.72 to -1.70)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.55
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.84
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.38
         upper limit
    		 2.47
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 3.51
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.46
         upper limit
    		 5.54

    Secondary: Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants

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    End point title
    		 Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants
    End point description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the lumbar spine at randomization, and at yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    1116
    1127
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=1116, 1127)
    4.56 (4.31 to 4.80)
    0.54 (0.29 to 0.78)
        Month 24 (n=1025, 1004)
    6.60 (6.31 to 6.90)
    0.82 (0.52 to 1.11)
        Month 36 (n=889, 853)
    8.49 (8.13 to 8.85)
    0.87 (0.50 to 1.23)
        Month 48 (n=63, 40)
    10.31 (9.34 to 11.29)
    0.80 (-0.40 to 2.00)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2243
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.67
         upper limit
    		 4.37
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2243
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.37
         upper limit
    		 6.2
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2243
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    7.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.11
         upper limit
    		 8.13
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2243
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.96
         upper limit
    		 11.06

    Secondary: Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants

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    End point title
    		 Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants
    End point description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the total hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    1127
    1155
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=1127, 1155)
    2.63 (2.43 to 2.83)
    0.24 (0.04 to 0.44)
        Month 24 (n=1035, 1020)
    3.56 (3.30 to 3.82)
    -0.64 (-0.90 to -0.39)
        Month 36 (n=889, 853)
    4.45 (4.14 to 4.76)
    -1.41 (-1.72 to -1.09)
        Month 48 (n=65, 42)
    4.07 (3.09 to 5.04)
    -4.47 (-5.67 to -3.27)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.11
         upper limit
    		 2.68
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.84
         upper limit
    		 4.57
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.41
         upper limit
    		 6.3
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7
         upper limit
    		 10.09

    Secondary: Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants

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    End point title
    		 Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants
    End point description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the femoral neck-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    1127
    1156
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=1127, 1156)
    2.71 (2.44 to 2.98)
    0.50 (0.24 to 0.77)
        Month 24 (n=1035, 1020)
    3.88 (3.56 to 4.19)
    -0.45 (-0.77 to -0.13)
        Month 36 (n=889, 853)
    5.12 (4.75 to 5.50)
    -0.97 (-1.35 to -0.59)
        Month 48 (n=65, 42)
    6.75 (5.43 to 8.08)
    -2.32 (-3.96 to -0.68)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2283
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.83
         upper limit
    		 2.59
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2283
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.87
         upper limit
    		 4.78
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2283
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.56
         upper limit
    		 6.62
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2283
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.97
         upper limit
    		 11.19

    Secondary: Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants

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    End point title
    		 Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants
    End point description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the trochanter-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    1127
    1155
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=1127, 1155)
    4.02 (3.70 to 4.35)
    0.58 (0.26 to 0.90)
        Month 24 (n=1035, 1020)
    5.73 (5.33 to 6.12)
    -0.30 (-0.70 to 0.10)
        Month 36 (n=889, 853)
    7.47 (6.99 to 7.94)
    -1.02 (-1.50 to -0.54)
        Month 48 (n=65, 42)
    6.68 (5.04 to 8.32)
    -5.07 (-7.09 to -3.05)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.98
         upper limit
    		 3.9
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.47
         upper limit
    		 6.59
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.81
         upper limit
    		 9.16
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    2282
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    11.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.15
         upper limit
    		 14.36

    Secondary: Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants

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    End point title
    		 Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants
    End point description
    BMD was measured by DXA at the distal one-third radius at rand. and at yearly intervals until the end of study (base study) in an approx. 10% random subset of bisphosphonate-intolerant participants at selected sites. Bisphosphontes are anti-resorptive agents used in treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindic. or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards signific. testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Month 60) or results should be viewed with caution as explor. results (i.e., Month 48). The FAS population including all rand. patients who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    77
    112
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=77, 112)
    0.99 (0.06 to 1.93)
    -0.09 (-0.87 to 0.69)
        Month 24 (n=71, 100)
    0.24 (-0.79 to 1.28)
    -0.80 (-1.67 to 0.06)
        Month 36 (n=64, 82)
    -0.66 (-1.76 to 0.44)
    -1.87 (-2.82 to -0.92)
        Month 48 (n=8, 5)
    -0.72 (-4.90 to 3.45)
    -2.27 (-7.23 to 2.68)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.083
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 2.31
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.129
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.31
         upper limit
    		 2.4
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.104
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.25
         upper limit
    		 2.67
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.617
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.92
         upper limit
    		 8.02

    Secondary: Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation

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    End point title
    		 Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation
    End point description
    s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (s-CTx) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 4 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    618
    629
    Units: ng/mL
    geometric mean (confidence interval 95%)
        Month 6 (n=571, 585)
    -61.27 (-63.33 to -59.09)
    -2.28 (-7.43 to 3.15)
        Month 12 (n=618, 629)
    -53.47 (-55.98 to -50.81)
    6.54 (0.85 to 12.56)
        Month 24 (n=528, 534)
    -39.47 (-42.61 to -36.15)
    7.23 (1.70 to 13.07)
        Month 36 (n=447, 414)
    -23.71 (-27.79 to -19.40)
    20.96 (14.38 to 27.91)
        Month 48 (n=55, 54)
    -4.61 (-15.93 to 8.24)
    14.12 (0.47 to 29.61)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1247
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -58.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -64.68
         upper limit
    		 -53.3
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1247
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -60.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -66.4
         upper limit
    		 -53.61
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1247
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -46.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -53.23
         upper limit
    		 -40.17
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1247
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -44.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -52.62
         upper limit
    		 -36.72
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1247
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.05
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -18.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -37.44
         upper limit
    		 -0.01

    Secondary: Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation

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    End point title
    		 Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation
    End point description
    u-NTx, a biochemical marker of bone resorption, was assessed at rand., Month 6, & at yearly intervals until end of study (base study) in an approx. 10% random subset participants at selected sites. Urine NTx measurements (in bone collagen equivalents [BCE]) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) & the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size). Back-transformed weighted geom. LS means values for percent change from baseline are provided. The per-protocol population incl. all rand. patients who took at least one dose of study medication and having the necessary on-treatment information (u-NTx/Cr) & excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 4 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    603
    619
    Units: nmol BCE/mmol
    geometric mean (confidence interval 95%)
        Month 6 (n=554, 569)
    -56.46 (-58.27 to -54.56)
    -4.76 (-8.68 to -0.67)
        Month 12 (n=603, 619)
    -55.58 (-57.54 to -53.53)
    -1.99 (-6.26 to 2.48)
        Month 24 (n=516, 516)
    -47.21 (-49.70 to -44.61)
    9.46 (4.33 to 14.85)
        Month 36 (n=438, 406)
    -43.91 (-46.80 to -40.86)
    15.23 (9.15 to 21.64)
        Month 48 (n=49, 52)
    -38.01 (-46.30 to -28.43)
    6.53 (-7.38 to 22.53)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -51.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -56.11
         upper limit
    		 -47.28
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -53.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.39
         upper limit
    		 -48.79
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -56.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -62.52
         upper limit
    		 -50.84
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -59.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -66.04
         upper limit
    		 -52.23
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -44.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -61.72
         upper limit
    		 -27.36

    Secondary: Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation

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    End point title
    		 Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation
    End point description
    BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at rand., Month 6, and at yearly intervals until the end of the study (base study) in an approx. 10% random subset participants at selected sites. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all rand. patients who took at least one dose of study medication and having the necessary on-treatment information (BSAP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 4 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    634
    650
    Units: ng/mL
    geometric mean (confidence interval 95%)
        Month 6 (n=594, 614)
    -23.27 (-25.12 to -21.38)
    -9.13 (-11.28 to -6.93)
        Month 12 (n=634, 650)
    -21.43 (-23.53 to -19.27)
    -9.42 (-11.80 to -6.97)
        Month 24 (n=543, 545)
    -9.33 (-12.10 to -6.47)
    -0.04 (-3.07 to 3.08)
        Month 36 (n=460, 433)
    -8.41 (-11.23 to -5.51)
    -0.77 (-3.85 to 2.40)
        Month 48 (n=59, 55)
    -0.63 (-8.39 to 7.80)
    0.15 (-7.93 to 8.94)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -14.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17
         upper limit
    		 -11.27
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -12.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.22
         upper limit
    		 -8.79
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -9.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.45
         upper limit
    		 -5.13
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -7.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.87
         upper limit
    		 -3.41
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.896
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.34
         upper limit
    		 10.79

    Secondary: Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation

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    End point title
    		 Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation
    End point description
    P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (P1NP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 4 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    634
    650
    Units: ng/mL
    geometric mean (confidence interval 95%)
        Month 6 (n=594, 613)
    -44.51 (-46.71 to -42.23)
    -15.08 (-18.39 to -11.65)
        Month 12 (n=634, 650)
    -37.49 (-40.12 to -34.75)
    -11.55 (-15.21 to -7.72)
        Month 24 (n=543, 545)
    -22.46 (-25.69 to -19.09)
    -6.20 (-10.08 to -2.16)
        Month 36 (n=460, 433)
    -11.89 (-15.70 to -7.92)
    0.22 (-4.15 to 4.78)
        Month 48 (n=59, 55)
    -3.61 (-12.04 to 5.62)
    -0.28 (-9.25 to 9.58)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -29.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.47
         upper limit
    		 -25.39
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -25.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.54
         upper limit
    		 -21.34
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -16.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.41
         upper limit
    		 -11.12
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -12.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.03
         upper limit
    		 -6.19
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.61
    Method
    		 Longitudinal
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.12
         upper limit
    		 9.45

    Secondary: Base Study + First Extension + Second Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture

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    End point title
    		 Base Study + First Extension + Second Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    End point description
    Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures occurring after baseline were confirmed by quantitative morphometric (QM) and either SQ or binary SQ methodologies. A time-to-event methodology was used: life-table estimates of the proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and at yearly intervals; an interval-censored approach was used to determine incidence rate (number of participants with a morphometric fracture per 100 patient-years of follow-up). The Full-Analysis-Set (FAS) including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) with at least one spine radiograph on treatment (and at baseline) was used for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 10 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    0 [4]
    0 [5]
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    Notes
    [4] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018
    [5] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018
    No statistical analyses for this end point

    Secondary: Second Extension: Incidence of Osteoporotic Clinical Thoracic Vertebral Fracture (Adjudicated)

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    End point title
    		 Second Extension: Incidence of Osteoporotic Clinical Thoracic Vertebral Fracture (Adjudicated)
    End point description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudic. using radiographic evidence on all symptomatic fractures reported as adverse experiences (excl. fractures of fingers, toes, face, & skull). Vertebral fractures were assessed for all thoracic vertebral levels (T1 to T12). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second ext. study with osteoporotic vertebral clinical fractures is provided. Due to early term. of the study, cumulative incidence using a time-to-event methodology was not assessed across base and ext. studies. The All-Participants-as-Treated Population including all rand. participants who entered the second ext. study & received at least one dose of open-label treatment was used for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 5 years (in the second extension)
    End point values
    		 Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Number of subjects analysed
    3144
    2309
    Units: Percentage of Participants
        number (not applicable)
    0.13
    0.09
    No statistical analyses for this end point

    Secondary: Second Extension: Incidence of Osteoporotic Clinical Lumbar Vertebral Fracture (Adjudicated)

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    End point title
    		 Second Extension: Incidence of Osteoporotic Clinical Lumbar Vertebral Fracture (Adjudicated)
    End point description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudic. using radiographic evidence on all symptomatic fractures reported as adverse experiences (excl. fractures of fingers, toes, face, & skull). Vertebral fractures were assessed for all lumbar vertebral levels (L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second ext. study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, cumulative incidence using a time-to-event methodology was not assessed across base and ext. studies. The All-Participants-as-Treated Population incl. all rand. participants who entered the second ext. study and received at least one dose of open-label treatment was used for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 5 years (in the second extension)
    End point values
    		 Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Number of subjects analysed
    3144
    2309
    Units: Percentage of Participants
        number (not applicable)
    0.22
    0.04
    No statistical analyses for this end point

    Secondary: Second Extension: Incidence of Osteoporotic Clinical Fracture of Any Type (Adjudicated)

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    End point title
    		 Second Extension: Incidence of Osteoporotic Clinical Fracture of Any Type (Adjudicated)
    End point description
    Osteoporotic clinical fractures of any type were confirmed by central adjudic. using radiogr. evidence on all symp. fractures reported as adverse experiences (excl. fractures of fingers, toes, face, skull). Non-vertebral fractures were assessed across mult. anat. sites incl. clavicle, dist. femur/shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, wrist; Vert. fractures assessed acr. all levels (C7/T1-12/L1-5) were incl. in analysis. Osteoporotic (fragility) fractures did not incl. fractures with traumatic/path. etiologies. Clin. fracture was defined as a fracture with related symptoms (eg, pain). The incid. proportion (cumul. incidence) of participants in 2nd ext. study with at least one osteoporotic clin. fracture of any type is provided. The All-Participants-as-Treated Popul. incl. all rand. participants who entered 2nd ext. study & received at least one dose of open-label treatment was used for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 5 years (in the second extension)
    End point values
    		 Odanacatib 50 mg OW Odanacatib 50 mg OW (originally assigned to Placebo)
    Number of subjects analysed
    3144
    2309
    Units: Percentage of Participants
        number (not applicable)
    2.04
    2.64
    No statistical analyses for this end point

    Secondary: Base Study + First Extension + Second Extension: Change in Height From Baseline Stature

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    End point title
    		 Base Study + First Extension + Second Extension: Change in Height From Baseline Stature
    End point description
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals across the base study and the two extension studies.
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 10 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    0 [6]
    0 [7]
    Units: cm
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [6] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018
    [7] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018
    No statistical analyses for this end point

    Secondary: Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Lumbar Spine

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    End point title
    		 Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Lumbar Spine
    End point description
    BMD was measured by DXA at lumbar spine starting at rand. & yearly interv. until end of study (2nd ext. study) for all participants who entered 2nd ext. study. Measurements were made on at least 3 vert. for all time points; vert. with fractures were excluded. At M96/108, approx. 3% or fewer patients in each tx group had BMD data & results at those time points should be viewed with caution. NOTE: Mean % change in BMD from baseline in participants originally rand. to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in base study. A longit. model with terms for tx, stratum, region & interaction b/w. tx & time as fixed effects (LS means weighted for region & stratum size) was used. The FAS popul. consisted of all rand. participants who entered 2nd ext. study & received at least one dose of open-label tx & had necessary on-tx info. (lumbar spine BMD).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 10 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    2818
    2128
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=2818, 2128)
    4.68 (4.54 to 4.83)
    1.01 (0.84 to 1.17)
        Month 24 (n=2803, 2121)
    6.95 (6.78 to 7.12)
    1.40 (1.21 to 1.59)
        Month 36 (n=2798, 2117)
    8.84 (8.65 to 9.04)
    1.61 (1.39 to 1.83)
        Month 48 (n=2754, 2077)
    10.74 (10.51 to 10.97)
    2.06 (1.80 to 2.33)
        Month 60 (n=2604, 1975)
    12.55 (12.29 to 12.81)
    2.45 (2.16 to 2.75)
        Month 72 (n=2068, 1594)
    13.76 (13.46 to 14.06)
    6.25 (5.91 to 6.59)
        Month 84 (n=1538, 1152)
    14.91 (14.56 to 15.26)
    8.37 (7.97 to 8.77)
        Month 96 (n=208, 177)
    15.13 (14.48 to 15.78)
    9.66 (8.95 to 10.38)
        Month 108 (n=56, 47)
    15.54 (14.23 to 16.85)
    10.85 (9.42 to 12.27)
    No statistical analyses for this end point

    Secondary: Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Femoral Neck

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    End point title
    		 Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Femoral Neck
    End point description
    BMD was measured by DXA at fem. neck starting at screening & yearly interv. until end of study (2nd ext. study) for all participants who entered 2nd ext. study. LS means % change in BMD from original baseline (BL) are provided through M108. At M96/108, approx. 3% or fewer patients in each tx group had BMD data & results at those time points should be viewed with caution. NOTE: The mean % change in BMD from BL in participants originally rand. to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in base study. A longit. model with terms for tx, stratum, region & interaction b/w tx & time as fixed effects (LS means weighted for region & stratum size) was used for analysis. The FAS popul. consisted of all rand. participants who entered 2nd ext. study & received at least 1 dose of open-label treatment & had necessary on-treatment info. (fem. neck BMD).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 10 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    2997
    2212
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=2997, 2212)
    2.89 (2.73 to 3.05)
    1.06 (0.88 to 1.24)
        Month 24 (n=2965, 2189)
    4.39 (4.20 to 4.57)
    0.38 (0.17 to 0.60)
        Month 36 (n=2950, 2171)
    6.02 (5.81 to 6.24)
    -0.03 (-0.28 to 0.22)
        Month 48 (n=2905, 2133)
    7.01 (6.78 to 7.25)
    -0.73 (-1.01 to -0.46)
        Month 60 (n=2718, 2015)
    7.98 (7.70 to 8.25)
    -1.32 (-1.63 to -1.00)
        Month 72 (n=2186, 1637)
    8.51 (8.21 to 8.81)
    0.41 (0.06 to 0.76)
        Month 84 (n=1631, 1197)
    9.11 (8.75 to 9.48)
    1.56 (1.13 to 1.98)
        Month 96 (n=237, 187)
    8.84 (8.22 to 9.46)
    1.95 (1.24 to 2.65)
        Month 108 (n=63, 51)
    9.38 (7.83 to 10.92)
    3.63 (1.91 to 5.35)
    No statistical analyses for this end point

    Secondary: Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Trochanter

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    End point title
    		 Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Trochanter
    End point description
    BMD was measured by DXA at the trochanter starting at screening & at yearly intervals until end of study (2nd ext. study) for all participants who entered the 2nd ext. study. LS means % change in BMD from original BL are provided through M108. At M96/108, approx. 3% or fewer patients in each tx group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean % change in BMD from BL in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in base study. A longit. model with terms for treatment, stratum, region & interaction b/w tx & time as fixed effects (LS means weighted for region & stratum size) was used. The FAS popul. consisted of all rand. participants who entered 2nd ext. study & received at least one dose of open-label tx & had the necessary on-tx info. (trochanter BMD).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 10 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    2997
    2212
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=2997, 2212)
    4.55 (4.34 to 4.75)
    1.81 (1.58 to 2.05)
        Month 24 (n=2965, 2189)
    6.85 (6.62 to 7.08)
    1.45 (1.18 to 1.72)
        Month 36 (n= 2950, 2171)
    9.00 (8.73 to 9.28)
    0.89 (0.57 to 1.21)
        Month 48 (n=2905, 2133)
    10.58 (10.26 to 10.89)
    -0.16 (-0.52 to 0.21)
        Month 60 (n= 2718, 2015)
    12.21 (11.85 to 12.57)
    -0.68 (-1.09 to -0.26)
        Month 72 (n=2186, 1637)
    12.95 (12.55 to 13.34)
    1.22 (0.76 to 1.68)
        Month 84 (n=1631, 1197)
    13.30 (12.82 to 13.78)
    3.17 (2.61 to 3.73)
        Month 96 (n=237, 187)
    13.44 (12.67 to 14.20)
    4.66 (3.79 to 5.54)
        Month 108 (n= 63, 51)
    12.69 (10.86 to 14.51)
    2.97 (0.95 to 5.00)
    No statistical analyses for this end point

    Secondary: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)

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    End point title
    		 Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
    End point description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study + first extension) was used for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    0.18
    0.56
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    The Cox proportional hazards model included terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 0.45

    Secondary: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Fracture (Adjudicated)

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    End point title
    		 Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Fracture (Adjudicated)
    End point description
    Osteoporotic clinical fractures (combining vertebral & non-vert.) were confirmed by central adjudic. using radiographic evidence on all symp. fractures reported as adverse experiences (excl. fractures of fingers, toes, face, skull). Vert. fractures were assessed for all levels (C7/T1-12/L1-5). Non-vert. fractures were assessed acr. multiple anat. sites incl. clav., distal femur/shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, wrist. Osteoporotic (fragility) fractures did not incl. fractures with traumatic or pathol. etiologies. A clin. fracture was defined as fracture with related symp. (eg, pain). A time-to-event methodol. was used to eval. results: the incid. rate of participants with fracture (# of participants with fracture per 100 patient-years of follow-up) is provided. The FAS incl. all rand. participants who took at least 1 dose of study medication with follow-up from start of prime therapy to study term. (base study + first ext.) was used for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part.with fracture per 100 patient-years
        number (not applicable)
    1.95
    2.93
    Statistical analysis title
    		 Odanacatib 50 mg OW vs Placebo.
    Statistical analysis description
    The Cox proportional hazards model included terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 0.75

    Secondary: Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Total Hip

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    End point title
    		 Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Total Hip
    End point description
    BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study + first extension-dbp).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6498
    6601
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=292, 302)
    1.89 (1.60 to 2.17)
    0.55 (0.26 to 0.83)
        Month 12 (n=6498, 6601)
    2.84 (2.75 to 2.92)
    0.34 (0.26 to 0.43)
        Month 24 (n=5924, 5899)
    3.79 (3.68 to 3.90)
    -0.67 (-0.78 to -0.57)
        Month 36 (n=5294, 5069)
    4.78 (4.65 to 4.92)
    -1.67 (-1.81 to -1.54)
        Month 48 (n=3806, 3338)
    5.52 (5.35 to 5.69)
    -2.97 (-3.14 to -2.79)
        Month 60 (n=3180, 2599)
    6.23 (6.02 to 6.44)
    -4.06 (-4.28 to -3.84)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 1.74
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.38
         upper limit
    		 2.62
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.31
         upper limit
    		 4.62
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.26
         upper limit
    		 6.65
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.24
         upper limit
    		 8.73
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.99
         upper limit
    		 10.59

    Secondary: Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Lumbar Spine

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    End point title
    		 Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Lumbar Spine
    End point description
    BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (lumbar spine BMD) was used for analysis (base study + first extension-dbp).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6220
    6375
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=291, 298)
    3.72 (3.36 to 4.07)
    0.82 (0.47 to 1.17)
        Month 12 (n=6220, 6375)
    4.61 (4.50 to 4.71)
    0.60 (0.49 to 0.70)
        Month 24 (n=5682, 5753)
    6.63 (6.50 to 6.76)
    0.70 (0.58 to 0.83)
        Month 36 (n=5105, 5008)
    8.41 (8.26 to 8.56)
    0.72 (0.56 to 0.87)
        Month 48 (n=3619, 3261)
    10.19 (10.01 to 10.38)
    0.85 (0.66 to 1.04)
        Month 60 (n=3066, 2547)
    11.93 (11.71 to 12.15)
    1.06 (0.83 to 1.29)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12595
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.4
         upper limit
    		 3.39
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12595
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.87
         upper limit
    		 4.15
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12595
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.75
         upper limit
    		 6.11
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12595
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    7.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.48
         upper limit
    		 7.91
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12595
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.08
         upper limit
    		 9.61
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    12595
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.55
         upper limit
    		 11.19

    Secondary: Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Femoral Neck

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    End point title
    		 Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Femoral Neck
    End point description
    BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study + first extension-dbp).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6498
    6601
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=292, 302)
    2.17 (1.78 to 2.55)
    0.70 (0.32 to 1.08)
        Month 12 (n=6498, 6601)
    2.81 (2.70 to 2.92)
    0.60 (0.49 to 0.71)
        Month 24 (n=5924, 5899)
    4.03 (3.90 to 4.16)
    -0.36 (-0.49 to -0.22)
        Month 36 (n=5294, 5069)
    5.48 (5.32 to 5.64)
    -1.02 (-1.18 to -0.86)
        Month 48 (n=3807, 3338)
    6.37 (6.17 to 6.56)
    -1.93 (-2.13 to -1.73)
        Month 60 (n=3181, 2599)
    7.30 (7.08 to 7.53)
    -2.75 (-2.99 to -2.51)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 2.01
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.05
         upper limit
    		 2.37
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.2
         upper limit
    		 4.57
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.28
         upper limit
    		 6.72
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.02
         upper limit
    		 8.57
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.72
         upper limit
    		 10.38

    Secondary: Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Trochanter

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    End point title
    		 Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Trochanter
    End point description
    BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study + first extension-dbp).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    6498
    6601
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 6 (n=292, 302)
    2.70 (2.21 to 3.18)
    0.95 (0.47 to 1.43)
        Month 12 (n=6498, 6601)
    4.33 (4.19 to 4.47)
    0.83 (0.69 to 0.97)
        Month 24 (n=5924, 5899)
    6.17 (6.00 to 6.34)
    -0.23 (-0.40 to -0.06)
        Month 36 (n=5294, 5069)
    7.96 (7.75 to 8.16)
    -1.29 (-1.50 to -1.08)
        Month 48 (n=3806, 3338)
    9.27 (9.01 to 9.53)
    -2.86 (-3.13 to -2.59)
        Month 60 (n=3180, 2599)
    10.66 (10.36 to 10.97)
    -3.90 (-4.22 to -3.57)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 6.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 2.42
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.31
         upper limit
    		 3.7
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.16
         upper limit
    		 6.65
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.95
         upper limit
    		 9.54
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    12.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.76
         upper limit
    		 12.51
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    13099
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    14.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.11
         upper limit
    		 15.01

    Secondary: Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Distal-Third Forearm

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    End point title
    		 Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Distal-Third Forearm
    End point description
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study + first extension-dbp) in an approximate 10% random subset of participants at selected sites. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study + first extension-dbp).
    End point type
    Secondary
    End point timeframe
    Baseline and once yearly up to 5 years
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    679
    718
    Units: g/cm^2
    least squares mean (confidence interval 95%)
        Month 12 (n=679, 718)
    0.50 (0.18 to 0.81)
    -0.61 (-0.91 to -0.30)
        Month 24 (n=619, 634)
    0.33 (-0.01 to 0.68)
    -1.02 (-1.37 to -0.68)
        Month 36 (n=576, 564)
    0.05 (-0.33 to 0.43)
    -1.91 (-2.29 to -1.53)
        Month 48 (n=251, 217)
    -0.30 (-0.84 to 0.23)
    -2.49 (-3.05 to -1.92)
        Month 60 (n=328, 263)
    -0.84 (-1.37 to -0.31)
    -3.17 (-3.74 to -2.59)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 12.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 1.54
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 24.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.85
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 36.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.42
         upper limit
    		 2.5
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 48.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.4
         upper limit
    		 2.96
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo at Month 60.
    Statistical analysis description
    The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    1397
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.54
         upper limit
    		 3.11

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
    End point description
    Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 24 was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip cortical vBMD) was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    51
    55
    Units: mg/cm^3
        least squares mean (confidence interval 95%)
    3.29 (2.33 to 4.24)
    0.52 (-0.39 to 1.44)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.43
         upper limit
    		 4.1

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in Areal BMD (aBMD) of the Lumbar Spine Using DXA

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in Areal BMD (aBMD) of the Lumbar Spine Using DXA
    End point description
    aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 24 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine aBMD) was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    50
    59
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    5.63 (4.54 to 6.72)
    0.08 (-0.92 to 1.09)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.06
         upper limit
    		 7.05

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Total Hip Using DXA

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Total Hip Using DXA
    End point description
    aBMD was measured at the total hip at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip aBMD) was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    49
    58
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    2.96 (2.03 to 3.90)
    -0.66 (-1.52 to 0.20)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.35
         upper limit
    		 4.9

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
    End point description
    aBMD was measured at the femoral neck at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (femoral neck aBMD) was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    49
    58
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    3.15 (1.74 to 4.56)
    0.36 (-0.94 to 1.65)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 4.72

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Trochanter Using DXA

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Trochanter Using DXA
    End point description
    aBMD was measured at the trochanter at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    49
    58
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    5.10 (3.74 to 6.45)
    -0.55 (-1.80 to 0.70)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.79
         upper limit
    		 7.5

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Distal-Third Forearm Using DXA

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Distal-Third Forearm Using DXA
    End point description
    aBMD was measured at the the distal one-third radius at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    49
    55
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    0.40 (-0.57 to 1.36)
    -1.27 (-2.18 to -0.36)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.016
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 3.01

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in s-CTx After Log-Transformation

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in s-CTx After Log-Transformation
    End point description
    s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (s-CTx) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    36
    45
    Units: ng/mL
        geometric mean (confidence interval 95%)
    -55.62 (-62.53 to -47.44)
    6.62 (-8.51 to 24.26)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -62.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -79.99
         upper limit
    		 -44.5

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in u-NTx/Cr Ratio After Log-Transformation

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in u-NTx/Cr Ratio After Log-Transformation
    End point description
    u-NTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline & M24 in an approx. 10% random subset participants at selected sites in P018 base study who were additionally included in imaging substudy PN032-base study. Urine NTx measurements (in BCE) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) & the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longit. model with terms for tx, stratum, & interaction b/w tx & time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for % change from baseline are provided. The per-protocol population incl. all rand. participants who took at least one dose of study medication & having necessary on-tx information (u-NTx/Cr) & excl. participants and/or data points that represent clinically important deviations from protocol-specified criteria was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    36
    45
    Units: nmol BCE/mmol
        geometric mean (confidence interval 95%)
    -47.87 (-57.26 to -36.42)
    16.56 (-2.85 to 39.84)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -64.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -87.8
         upper limit
    		 -41.07

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in BSAP After Log-Transformation

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in BSAP After Log-Transformation
    End point description
    BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at baseline & M24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for tx, stratum, & interaction between tx & time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population incl. all rand. patients who took at least one dose of study medication & having the necessary on-tx information (BSAP) & excl. participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    36
    45
    Units: ng/mL
        geometric mean (confidence interval 95%)
    -12.39 (-19.20 to -4.99)
    12.64 (4.53 to 21.38)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -25.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.92
         upper limit
    		 -14.12

    Secondary: Imaging Substudy PN032-Base: Percent Change From Baseline in P1NP After Log-Transformation

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    End point title
    		 Imaging Substudy PN032-Base: Percent Change From Baseline in P1NP After Log-Transformation
    End point description
    P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at baseline and Month 24 in an approx. 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction change from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, & interaction b/w treatment & time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for % change from baseline are provided. The per-protocol population including all rand. patients who took at least one dose of study medication & having the necessary on-treatment information (P1NP) & excl. participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    36
    45
    Units: ng/mL
        geometric mean (confidence interval 95%)
    -33.56 (-42.66 to -23.01)
    -6.86 (-18.71 to 6.72)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -26.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.56
         upper limit
    		 -10.83

    Secondary: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography

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    End point title
    		 Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
    End point description
    Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip cortical vBMD) was used for analysis (PN032-Base).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 60
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    32
    27
    Units: mg/cm^3
        least squares mean (confidence interval 95%)
    6.00 (4.07 to 7.93)
    -2.53 (-4.48 to -0.59)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.79
         upper limit
    		 11.28

    Secondary: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Lumbar Spine Using DXA

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    End point title
    		 Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Lumbar Spine Using DXA
    End point description
    aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 60 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine aBMD) was used for analysis (PN032-Base + Extension).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 60
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    36
    37
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    11.80 (9.86 to 13.73)
    0.72 (-1.10 to 2.54)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    11.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.41
         upper limit
    		 13.74

    Secondary: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Total Hip Using DXA

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    End point title
    		 Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Total Hip Using DXA
    End point description
    aBMD was measured at the total hip at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip aBMD) was used for analysis (PN032-Base + Extension).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 60
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    38
    35
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    5.34 (3.66 to 7.01)
    -5.07 (-6.74 to -3.41)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.05
         upper limit
    		 12.78

    Secondary: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA

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    End point title
    		 Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
    End point description
    aBMD was measured at the femoral neck at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (femoral neck aBMD) was used for analysis (PN032-Base + Extension).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 60
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    38
    35
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    6.87 (4.68 to 9.06)
    -3.11 (-5.26 to -0.96)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.91
         upper limit
    		 13.06

    Secondary: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Trochanter Using DXA

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    End point title
    		 Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Trochanter Using DXA
    End point description
    aBMD was measured at the trochanter at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base + Extension).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 60
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    38
    35
    Units: g/cm^2
        least squares mean (confidence interval 95%)
    10.44 (7.84 to 13.03)
    -4.50 (-7.07 to -1.94)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Longitudinal model
    Parameter type
    		 Mean difference (final values)
    Point estimate
    14.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.29
         upper limit
    		 18.59

    Secondary: Base Study: Time to First 4-Point MACE Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First 4-Point MACE Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    1.25
    1.12
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.181
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.32

    Secondary: Base Study: Time to First All-Cause Death Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First All-Cause Death Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated all-cause death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    1.56
    1.38
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region.
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.102
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.3

    Secondary: Base Study: Time to First Cardiovascular Death Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First Cardiovascular Death Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated cardiovascular death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.45
    0.38
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.277
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.52

    Secondary: Base Study: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.25
    0.31
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.256
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 1.15

    Secondary: Base Study: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.03
    0.03
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.794
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 2.57

    Secondary: Base Study: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.58
    0.44
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.034
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.7

    Secondary: Base Study: Time to First Fatal Stroke Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First Fatal Stroke Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.09
    0.05
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.081
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 3.97

    Secondary: Base Study: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.10
    0.09
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.857
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.89

    Secondary: Base Study: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.25
    0.23
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.606
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.59

    Secondary: Base Study: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication

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    End point title
    		 Base Study: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.60
    0.48
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.074
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.6

    Secondary: Base Study + First Extension: Time to First 4-Point MACE Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First 4-Point MACE Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    1.31
    1.15
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.062
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.31

    Secondary: Base Study + First Extension: Time to First All-Cause Death Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First All-Cause Death Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated all-cause death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    1.79
    1.70
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.341
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.17

    Secondary: Base Study + First Extension: Time to First Cardiovascular Death Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First Cardiovascular Death Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated cardiovascular death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.48
    0.43
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.246
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.4

    Secondary: Base Study + First Extension: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.26
    0.28
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.675
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.26

    Secondary: Base Study + First Extension: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.02
    0.03
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.638
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 2.03

    Secondary: Base Study + First Extension: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.58
    0.42
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 1.71

    Secondary: Base Study + First Extension: Time to First Fatal Stroke Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First Fatal Stroke Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.09
    0.05
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.114
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 2.9

    Secondary: Base Study + First Extension: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.08
    0.10
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.366
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.33

    Secondary: Base Study + First Extension: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.27
    0.22
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.198
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.68

    Secondary: Base Study + First Extension: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication

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    End point title
    		 Base Study + First Extension: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    End point description
    The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
    End point type
    Secondary
    End point timeframe
    Up to 5 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (not applicable)
    0.61
    0.50
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Statistical analysis description
    Cox proportional hazards model with terms for treatment, stratum and geographic region
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.059
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.5

    Post-hoc: Base Study: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication

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    End point title
    		 Base Study: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication
    End point description
    The incidence rate of femoral shaft fracture events (including both atypical and non-atypical; of any etiology including traumatic) confirmed by adjudication was determined for the base study. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study).
    End point type
    Post-hoc
    End point timeframe
    Up to 4 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    0.10 (0.06 to 0.15)
    0.06 (0.03 to 0.10)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in rates
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.01
         upper limit
    		 0.09

    Post-hoc: Base Study: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication

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    End point title
    		 Base Study: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication
    End point description
    Atypical subtrochanteric/diaphyseal femoral fractures (AFF) are an uncommon type of low-energy (eg, osteoporotic) femoral shaft fracture of unclear causation infrequently reported in osteoporotic persons treated with long-term anti-resorptive therapy (eg, bisphosphonates). All femoral (femur, femur-distal, femur-shaft) fractures in the base study were adjudicated against both ASBMR 2010 and 2013 criteria . All 5 major features (ie, location along femoral shaft, no/minimal trauma, transverse/short oblique fracture, non-comminuted, complete/incomplete fracture) were required for ASBMR 2010 AFF case definition; while 4 of 5 major features (ie, no/minimal trauma, substantially transverse orientation at cortical origin with possible oblique orientation medially, non-comminuted/minimally comminuted, complete/incomplete fracture, localized periosteal reaction of lateral cortex) with requirement for location along femoral shaft were required for ASBMR 2013 AFF case definition.
    End point type
    Post-hoc
    End point timeframe
    Up to 4 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    0.02 (0.01 to 0.05)
    0.00 (0.00 to 0.02)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in rates
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.05

    Post-hoc: Base Study + First Extension: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication

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    End point title
    		 Base Study + First Extension: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication
    End point description
    The incidence rate of femoral shaft fracture events (including both atypical and non-atypical; of any etiology including traumatic) confirmed by adjudication was determined for the base study + first extension. Results are expressed as number of participants with an event per 100 patient-years of follow-up.
    End point type
    Post-hoc
    End point timeframe
    Up to 4 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    0.09 (0.06 to 0.13)
    0.02 (0.01 to 0.05)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in rates
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 0.11

    Post-hoc: Base Study + First Extension: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication

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    End point title
    		 Base Study + First Extension: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication
    End point description
    Atypical subtrochanteric/diaphyseal femoral fractures (AFF) are an uncommon type of low-energy (eg, osteoporotic) femoral shaft fracture of unclear causation infrequently reported in osteoporotic persons treated with long-term anti-resorptive therapy (eg, bisphosphonates). All femoral (femur, femur-distal, femur-shaft) fractures in the base study + first extension were adjudicated against both ASBMR 2010 & 2013 criteria. All 5 major features (ie, location along femoral shaft, no/minimal trauma, transverse/short oblique fracture, non-comminuted, complete/incomplete fracture) were required for ASBMR 2010 AFF case definition; while 4 of 5 major features (ie, no/minimal trauma, substantially transverse orientation at cortical origin with possible oblique orientation medially, non-comminuted/minimally comminuted, complete/incomplete fracture, localized periosteal reaction of lateral cortex) with requirement for location along femoral shaft were required for ASBMR 2013 AFF case definition.
    End point type
    Post-hoc
    End point timeframe
    Up to 4 years (Data cutoff April 2016)
    End point values
    		 Odanacatib 50 mg OW Placebo
    Number of subjects analysed
    8043
    8028
    Units: Part. with event per 100 patient-years
        number (confidence interval 95%)
    0.03 (0.02 to 0.06)
    0.00 (0.00 to 0.01)
    Statistical analysis title
    		 Odanacatib 50 mg OW - Placebo
    Comparison groups
    Odanacatib 50 mg OW v Placebo
    Number of subjects included in analysis
    16071
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in rates
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 0.06

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 10 years
    Adverse event reporting additional description
    The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Base Study + First Extension: Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Base Study + First Extension: Placebo
    Reporting group description
    		 Participants receive blinded placebo to 10 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Second Extension: Odanacatib 50 mg OW
    Reporting group description
    		 Participants receive 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received 50 mg of blinded odanacatib weekly in the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Reporting group title
    Second Extension: Odanacatib 50 mg OW (Placebo)
    Reporting group description
    		 Participants receive 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received blinded placebo to 50 mg of odanacatib weekly in the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Serious adverse events
    		 Base Study + First Extension: Odanacatib 50 mg OW Base Study + First Extension: Placebo Second Extension: Odanacatib 50 mg OW Second Extension: Odanacatib 50 mg OW (Placebo)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2441 / 8043 (30.35%)
    2446 / 8028 (30.47%)
    508 / 3144 (16.16%)
    376 / 2309 (16.28%)
         number of deaths (all causes)
    378
    327
    86
    39
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Abdominal neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Acute leukaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    4 / 8043 (0.05%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    Adenocarcinoma of appendix
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    10 / 8043 (0.12%)
    7 / 8028 (0.09%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    Adenocarcinoma of the cervix
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angiosarcoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Astrocytoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    79 / 8043 (0.98%)
    71 / 8028 (0.88%)
    9 / 3144 (0.29%)
    8 / 2309 (0.35%)
         occurrences causally related to treatment / all
    0 / 93
    0 / 87
    0 / 10
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign gastric neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign breast neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign lung neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign muscle neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of bladder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of skin
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign salivary gland neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign vulval neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct cancer
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Borderline mucinous tumour of ovary
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bowen's disease
         subjects affected / exposed
    6 / 8043 (0.07%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain cancer metastatic
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    33 / 8043 (0.41%)
    32 / 8028 (0.40%)
    4 / 3144 (0.13%)
    9 / 2309 (0.39%)
         occurrences causally related to treatment / all
    0 / 33
    0 / 32
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer in situ
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer recurrent
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Breast cancer stage III
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchioloalveolar carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carcinoid tumour of the stomach
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carcinoma in situ of skin
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac myxoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar tumour
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellopontine angle tumour
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix cancer metastatic
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    6 / 8043 (0.07%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma recurrent
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma stage II
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Chondroma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Choroid melanoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    3 / 8043 (0.04%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clear cell endometrial carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    23 / 8043 (0.29%)
    17 / 8028 (0.21%)
    4 / 3144 (0.13%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 17
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    Colon neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Colorectal cancer recurrent
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma stage IV
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ductal adenocarcinoma of pancreas
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysplastic naevus
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    4 / 8043 (0.05%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Essential thrombocythaemia
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fallopian tube cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Female reproductive neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Fibroadenoma of breast
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibromatosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibroma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Follicle centre lymphoma, follicular grade I, II, III stage II
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder adenocarcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gallbladder cancer
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    5 / 8043 (0.06%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
    Gastric cancer stage IV
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastric neoplasm
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gastrointestinal neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gingival cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomus tumour
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemangioma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemangioma of bone
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    5 / 8043 (0.06%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    0 / 1
    0 / 1
    Hepatic neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Inflammatory carcinoma of the breast
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Intraductal papilloma of breast
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraocular melanoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    7 / 8043 (0.09%)
    5 / 8028 (0.06%)
    3 / 3144 (0.10%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive lobular breast carcinoma
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kaposi's sarcoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratoacanthoma
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leiomyoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leiomyosarcoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lentigo maligna
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lip and/or oral cavity cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lip squamous cell carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liposarcoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lobular breast carcinoma in situ
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    8 / 8043 (0.10%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma stage I
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma stage IV
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    2 / 8043 (0.02%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    13 / 8043 (0.16%)
    23 / 8028 (0.29%)
    4 / 3144 (0.13%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 24
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 6
    0 / 5
    0 / 2
    0 / 1
    Lymphangioma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lymphoproliferative disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    6 / 8043 (0.07%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma in situ
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm of ampulla of Vater
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm of eyelid
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm of renal pelvis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Malignant neoplasm of unknown primary site
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Malignant peritoneal neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mantle cell lymphoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medullary thyroid cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melanocytic naevus
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melanoma recurrent
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesothelioma
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesothelioma malignant
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metaplastic breast carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to pleura
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to skin
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastasis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastatic bronchial carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastatic gastric cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastatic malignant melanoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    Metastatic salivary gland cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic uterine cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mixed adenoneuroendocrine carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucinous breast carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mycosis fungoides
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome transformation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myeloproliferative disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal cavity cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Nasal neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngeal cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    Neuroendocrine carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Neuroendocrine carcinoma metastatic
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer metastatic
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Non-small cell lung cancer stage IV
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    Oesophageal squamous cell carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oligodendroglioma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Osteoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteosarcoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ovarian adenoma
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    7 / 8043 (0.09%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    Ovarian cancer metastatic
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Ovarian epithelial cancer stage I
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    13 / 8043 (0.16%)
    9 / 8028 (0.11%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 9
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 7
    0 / 6
    0 / 2
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    Pancreatic carcinoma stage IV
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Papillary serous endometrial carcinoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papilloma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritoneal mesothelioma malignant
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    6 / 8043 (0.07%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plasmacytoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Primary myelofibrosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyogenic granuloma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Rectal adenoma
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectosigmoid cancer
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Refractory anaemia with an excess of blasts
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Refractory cytopenia with unilineage dysplasia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    3 / 8043 (0.04%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma stage II
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal oncocytoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salivary gland cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Schwannoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    5 / 8043 (0.06%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer limited stage
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord neoplasm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Splenic marginal zone lymphoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    14 / 8043 (0.17%)
    12 / 8028 (0.15%)
    4 / 3144 (0.13%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 12
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    18 / 8043 (0.22%)
    10 / 8028 (0.12%)
    3 / 3144 (0.10%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 10
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the cervix
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Superficial spreading melanoma stage unspecified
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    T-cell lymphoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Thymoma malignant
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid adenoma
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer metastatic
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell cancer of the renal pelvis and ureter
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ureteric cancer
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    7 / 8043 (0.09%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine neoplasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulval cancer
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulval cancer stage 0
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Urethral cancer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the vagina
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    8 / 8043 (0.10%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm rupture
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    Aortic arteriosclerosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Arterial disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    5 / 8043 (0.06%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Bleeding varicose vein
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood pressure fluctuation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    2 / 8043 (0.02%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    17 / 8043 (0.21%)
    9 / 8028 (0.11%)
    1 / 3144 (0.03%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 9
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Distributive shock
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Essential hypertension
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iliac artery embolism
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Femoral artery occlusion
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    5 / 8043 (0.06%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hot flush
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    31 / 8043 (0.39%)
    37 / 8028 (0.46%)
    2 / 3144 (0.06%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    1 / 34
    0 / 39
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    10 / 8043 (0.12%)
    20 / 8028 (0.25%)
    4 / 3144 (0.13%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 21
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    Hypertensive emergency
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hypotension
         subjects affected / exposed
    7 / 8043 (0.09%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infarction
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Necrosis ischaemic
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    5 / 8043 (0.06%)
    4 / 8028 (0.05%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    7 / 8043 (0.09%)
    5 / 8028 (0.06%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral circulatory failure
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Subgaleal haematoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Temporal arteritis
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose ulceration
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    8 / 8043 (0.10%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Accidental death
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
    Adverse event
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    7 / 8043 (0.09%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    Capsular contracture associated with breast implant
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    22 / 8043 (0.27%)
    24 / 8028 (0.30%)
    3 / 3144 (0.10%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 25
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cyst
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    66 / 8043 (0.82%)
    62 / 8028 (0.77%)
    14 / 3144 (0.45%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    0 / 66
    0 / 62
    0 / 14
    0 / 4
         deaths causally related to treatment / all
    0 / 66
    0 / 62
    0 / 14
    0 / 4
    Device adhesion issue
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device breakage
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device damage
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    4 / 8043 (0.05%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device material issue
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug intolerance
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug withdrawal syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial pain
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General symptom
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ill-defined disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Implant site reaction
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multi-organ disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    10 / 8043 (0.12%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 9
    0 / 6
    0 / 0
    0 / 0
    Nodule
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    5 / 8043 (0.06%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    4 / 8043 (0.05%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral administration complication
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 8043 (0.05%)
    7 / 8028 (0.09%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue inflammation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Strangulated hernia
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    15 / 8043 (0.19%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 15
    0 / 2
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Organ failure
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Immobile
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adnexal torsion
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adnexa uteri mass
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anisomastia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast mass
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical dysplasia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical polyp
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colpocele
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystocele
         subjects affected / exposed
    7 / 8043 (0.09%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital labial adhesions
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrometra
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    12 / 8043 (0.15%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 5
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic floor muscle weakness
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic prolapse
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postmenopausal haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectocele
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal polyp
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    14 / 8043 (0.17%)
    13 / 8028 (0.16%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 14
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal fistula
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    7 / 8043 (0.09%)
    10 / 8028 (0.12%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulval leukoplakia
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulvar dysplasia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical leukoplakia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital prolapse
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    3 / 8043 (0.04%)
    9 / 8028 (0.11%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    4 / 8043 (0.05%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
    0 / 1
    Aspiration
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Asthma
         subjects affected / exposed
    10 / 8043 (0.12%)
    17 / 8028 (0.21%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 20
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    2 / 8043 (0.02%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    34 / 8043 (0.42%)
    36 / 8028 (0.45%)
    9 / 3144 (0.29%)
    5 / 2309 (0.22%)
         occurrences causally related to treatment / all
    0 / 43
    0 / 44
    0 / 11
    0 / 6
         deaths causally related to treatment / all
    0 / 5
    0 / 5
    0 / 1
    0 / 1
    Bronchospasm
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic respiratory disease
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 8043 (0.07%)
    6 / 8028 (0.07%)
    2 / 3144 (0.06%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eosinophilic pneumonia chronic
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epiglottic cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    6 / 8043 (0.07%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Laryngeal dysplasia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal granuloma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung consolidation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal polyp
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    Mediastinal cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal polyps
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Oesophagobronchial fistula
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal pouch
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pickwickian syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    13 / 8043 (0.16%)
    8 / 8028 (0.10%)
    3 / 3144 (0.10%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 8
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    6 / 8043 (0.07%)
    5 / 8028 (0.06%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 2
    0 / 1
    Pneumonitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    5 / 8043 (0.06%)
    3 / 8028 (0.04%)
    4 / 3144 (0.13%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Pulmonary arteriopathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    28 / 8043 (0.35%)
    28 / 8028 (0.35%)
    7 / 3144 (0.22%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 29
    0 / 30
    0 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 7
    0 / 9
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    8 / 8043 (0.10%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    3 / 8043 (0.04%)
    6 / 8028 (0.07%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    Pulmonary ossification
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    13 / 8043 (0.16%)
    9 / 8028 (0.11%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 9
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 7
    0 / 6
    0 / 1
    0 / 1
    Respiratory tract inflammation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus polyp
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus polyp degeneration
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Throat irritation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheal stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vocal cord disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vocal cord polyp
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety disorder
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety disorder due to a general medical condition
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Compulsive hoarding
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    4 / 8043 (0.05%)
    3 / 8028 (0.04%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    10 / 8043 (0.12%)
    10 / 8028 (0.12%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 10
    1 / 10
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysthymic disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mood disorder due to a general medical condition
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychogenic pain disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychogenic seizure
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood calcium decreased
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood cortisol increased
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood parathyroid hormone increased
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coagulation time prolonged
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram abnormal
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Grip strength decreased
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heart rate irregular
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    International normalised ratio decreased
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial necrosis marker increased
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Occult blood positive
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Residual urine volume increased
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anastomotic leak
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    13 / 8043 (0.16%)
    19 / 8028 (0.24%)
    4 / 3144 (0.13%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 23
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Arterial injury
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial restenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthropod bite
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical femur fracture
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone contusion
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone fissure
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac valve rupture
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chillblains
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    5 / 8043 (0.06%)
    8 / 8028 (0.10%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Compression fracture
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    6 / 8043 (0.07%)
    8 / 8028 (0.10%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    5 / 8043 (0.06%)
    15 / 8028 (0.19%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 18
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Excoriation
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug dispensing error
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    5 / 8043 (0.06%)
    2 / 8028 (0.02%)
    2 / 3144 (0.06%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    29 / 8043 (0.36%)
    62 / 8028 (0.77%)
    4 / 3144 (0.13%)
    9 / 2309 (0.39%)
         occurrences causally related to treatment / all
    0 / 29
    0 / 64
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    44 / 8043 (0.55%)
    40 / 8028 (0.50%)
    8 / 3144 (0.25%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    1 / 49
    0 / 41
    0 / 8
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Fibula fracture
         subjects affected / exposed
    11 / 8043 (0.14%)
    10 / 8028 (0.12%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 10
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    5 / 8043 (0.06%)
    9 / 8028 (0.11%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 9
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fractured ischium
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    8 / 8043 (0.10%)
    13 / 8028 (0.16%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 13
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Heat illness
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heat exhaustion
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heat stroke
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    55 / 8043 (0.68%)
    104 / 8028 (1.30%)
    6 / 3144 (0.19%)
    6 / 2309 (0.26%)
         occurrences causally related to treatment / all
    0 / 56
    0 / 105
    1 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    28 / 8043 (0.35%)
    51 / 8028 (0.64%)
    2 / 3144 (0.06%)
    7 / 2309 (0.30%)
         occurrences causally related to treatment / all
    0 / 29
    0 / 51
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Jaw fracture
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    6 / 8043 (0.07%)
    6 / 8028 (0.07%)
    2 / 3144 (0.06%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    6 / 8043 (0.07%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb crushing injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb traumatic amputation
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    13 / 8043 (0.16%)
    25 / 8028 (0.31%)
    6 / 3144 (0.19%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 27
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Muscle injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nerve root injury lumbar
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    8 / 8043 (0.10%)
    11 / 8028 (0.14%)
    5 / 3144 (0.16%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 11
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Post procedural discomfort
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural fistula
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural inflammation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural swelling
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural oedema
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post-traumatic neck syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative adhesion
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative hernia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural nausea
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    11 / 8043 (0.14%)
    7 / 8028 (0.09%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 7
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary contusion
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    66 / 8043 (0.82%)
    77 / 8028 (0.96%)
    3 / 3144 (0.10%)
    6 / 2309 (0.26%)
         occurrences causally related to treatment / all
    0 / 68
    0 / 79
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    7 / 8043 (0.09%)
    10 / 8028 (0.12%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 10
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scar
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin abrasion
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin wound
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fractured base
         subjects affected / exposed
    4 / 8043 (0.05%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord injury cervical
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sternal injury
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    6 / 8043 (0.07%)
    5 / 8028 (0.06%)
    3 / 3144 (0.10%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Synovial rupture
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    12 / 8043 (0.15%)
    23 / 8028 (0.29%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 28
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    13 / 8043 (0.16%)
    22 / 8028 (0.27%)
    3 / 3144 (0.10%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 22
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic shock
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    15 / 8043 (0.19%)
    28 / 8028 (0.35%)
    3 / 3144 (0.10%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 28
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulnar nerve injury
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    2 / 8043 (0.02%)
    6 / 8028 (0.07%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular injury
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    5 / 8043 (0.06%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    6 / 8043 (0.07%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital bronchiectasis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital cystic kidney disease
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Exomphalos
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroglossal cyst
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute left ventricular failure
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    55 / 8043 (0.68%)
    55 / 8028 (0.69%)
    17 / 3144 (0.54%)
    9 / 2309 (0.39%)
         occurrences causally related to treatment / all
    2 / 57
    0 / 59
    0 / 17
    0 / 9
         deaths causally related to treatment / all
    0 / 16
    0 / 14
    0 / 8
    0 / 4
    Adams-Stokes syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    39 / 8043 (0.48%)
    41 / 8028 (0.51%)
    4 / 3144 (0.13%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 44
    0 / 44
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    34 / 8043 (0.42%)
    34 / 8028 (0.42%)
    4 / 3144 (0.13%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    0 / 43
    1 / 37
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    5 / 8043 (0.06%)
    6 / 8028 (0.07%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    4 / 8043 (0.05%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    73 / 8043 (0.91%)
    80 / 8028 (1.00%)
    17 / 3144 (0.54%)
    10 / 2309 (0.43%)
         occurrences causally related to treatment / all
    0 / 83
    0 / 97
    0 / 23
    0 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    4 / 8043 (0.05%)
    6 / 8028 (0.07%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    8 / 8043 (0.10%)
    6 / 8028 (0.07%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 6
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    5 / 8043 (0.06%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular dissociation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    10 / 8043 (0.12%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block bilateral
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block right
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    10 / 8043 (0.12%)
    9 / 8028 (0.11%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 10
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    9 / 8043 (0.11%)
    13 / 8028 (0.16%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 13
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 6
    0 / 12
    0 / 2
    0 / 0
    Cardiac disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    35 / 8043 (0.44%)
    41 / 8028 (0.51%)
    7 / 3144 (0.22%)
    5 / 2309 (0.22%)
         occurrences causally related to treatment / all
    0 / 38
    0 / 44
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 9
    0 / 9
    0 / 5
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    7 / 8043 (0.09%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    37 / 8043 (0.46%)
    35 / 8028 (0.44%)
    10 / 3144 (0.32%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 38
    2 / 36
    0 / 10
    0 / 5
         deaths causally related to treatment / all
    0 / 8
    0 / 5
    0 / 2
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    11 / 8043 (0.14%)
    14 / 8028 (0.17%)
    4 / 3144 (0.13%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 14
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 11
    0 / 11
    0 / 4
    0 / 1
    Cardiogenic shock
         subjects affected / exposed
    5 / 8043 (0.06%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 5
    0 / 3
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    Cardiovascular disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    31 / 8043 (0.39%)
    25 / 8028 (0.31%)
    7 / 3144 (0.22%)
    6 / 2309 (0.26%)
         occurrences causally related to treatment / all
    0 / 34
    1 / 28
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Cor pulmonale acute
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery perforation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytotoxic cardiomyopathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extrasystoles
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heart valve incompetence
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive cardiomyopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Microvascular coronary artery disease
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    47 / 8043 (0.58%)
    48 / 8028 (0.60%)
    4 / 3144 (0.13%)
    5 / 2309 (0.22%)
         occurrences causally related to treatment / all
    0 / 50
    0 / 51
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 16
    0 / 19
    0 / 2
    0 / 1
    Myocardial ischaemia
         subjects affected / exposed
    19 / 8043 (0.24%)
    12 / 8028 (0.15%)
    1 / 3144 (0.03%)
    6 / 2309 (0.26%)
         occurrences causally related to treatment / all
    0 / 21
    0 / 12
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
    Myocarditis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pericardial haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Postinfarction angina
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prinzmetal angina
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    8 / 8043 (0.10%)
    9 / 8028 (0.11%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    4 / 8043 (0.05%)
    4 / 8028 (0.05%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 4
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia paroxysmal
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Ventricular dysfunction
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Altered state of consciousness
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Amnesia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amyotrophic lateral sclerosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Apallic syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal ganglia haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Basal ganglia infarction
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain stem stroke
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid arteriosclerosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery aneurysm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery disease
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    4 / 8043 (0.05%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid sinus syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    9 / 8043 (0.11%)
    5 / 8028 (0.06%)
    2 / 3144 (0.06%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 5
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar ischaemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral arteriosclerosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral artery embolism
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral circulatory failure
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    9 / 8028 (0.11%)
    2 / 3144 (0.06%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 9
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 5
    0 / 2
    0 / 2
    Cerebral infarction
         subjects affected / exposed
    31 / 8043 (0.39%)
    18 / 8028 (0.22%)
    1 / 3144 (0.03%)
    5 / 2309 (0.22%)
         occurrences causally related to treatment / all
    2 / 32
    0 / 18
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    5 / 8043 (0.06%)
    8 / 8028 (0.10%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 9
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral venous thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    68 / 8043 (0.85%)
    42 / 8028 (0.52%)
    8 / 3144 (0.25%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    2 / 68
    1 / 43
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 9
    0 / 8
    0 / 2
    0 / 1
    Cerebrovascular disorder
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Cerebrovascular insufficiency
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical myelopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Complex partial seizures
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cranial nerve disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    2 / 8043 (0.02%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    5 / 8043 (0.06%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    8 / 8043 (0.10%)
    7 / 8028 (0.09%)
    1 / 3144 (0.03%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    3 / 10
    0 / 7
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyslalia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolic cerebral infarction
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    6 / 8043 (0.07%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frontotemporal dementia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Haemorrhagic stroke
         subjects affected / exposed
    10 / 8043 (0.12%)
    6 / 8028 (0.07%)
    4 / 3144 (0.13%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 6
    0 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 8
    0 / 2
    0 / 4
    0 / 0
    Headache
         subjects affected / exposed
    5 / 8043 (0.06%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 5
    1 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    4 / 8043 (0.05%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertonia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic coma
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic unconsciousness
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    IVth nerve paralysis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Intracranial haematoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial venous sinus thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic neuropathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    39 / 8043 (0.48%)
    40 / 8028 (0.50%)
    21 / 3144 (0.67%)
    7 / 2309 (0.30%)
         occurrences causally related to treatment / all
    0 / 40
    0 / 41
    0 / 22
    1 / 7
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
    0 / 1
    Lacunar infarction
         subjects affected / exposed
    4 / 8043 (0.05%)
    8 / 8028 (0.10%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    6 / 8043 (0.07%)
    8 / 8028 (0.10%)
    4 / 3144 (0.13%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Memory impairment
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningorrhagia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Morton's neuralgia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Motor neurone disease
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nerve root compression
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuritis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parkinsonism
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral nerve lesion
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    4 / 8043 (0.05%)
    4 / 8028 (0.05%)
    2 / 3144 (0.06%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radicular syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ruptured cerebral aneurysm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    3 / 8043 (0.04%)
    6 / 8028 (0.07%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sedation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    5 / 8043 (0.06%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Senile dementia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Sensory disturbance
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Slow speech
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    3 / 8043 (0.04%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    31 / 8043 (0.39%)
    20 / 8028 (0.25%)
    4 / 3144 (0.13%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    0 / 33
    0 / 20
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Thalamus haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombotic stroke
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Transient global amnesia
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    31 / 8043 (0.39%)
    35 / 8028 (0.44%)
    2 / 3144 (0.06%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    2 / 33
    0 / 38
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VIIth nerve paralysis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular dementia
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular encephalopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral artery stenosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    2 / 8043 (0.02%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White matter lesion
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    16 / 8043 (0.20%)
    21 / 8028 (0.26%)
    4 / 3144 (0.13%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 22
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia megaloblastic
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia vitamin B12 deficiency
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aplastic anaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic diathesis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypochromic anaemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune thrombocytopenic purpura
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    4 / 8043 (0.05%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polycythaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pernicious anaemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Acute vestibular syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deafness neurosensory
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    External ear disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inner ear disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniere's disease
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurosensory hypoacusis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden hearing loss
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otosclerosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tinnitus
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    15 / 8043 (0.19%)
    5 / 8028 (0.06%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 16
    0 / 5
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tympanic membrane perforation
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    5 / 8043 (0.06%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Age-related macular degeneration
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amaurosis fugax
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angle closure glaucoma
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blindness
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blindness unilateral
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract nuclear
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    98 / 8043 (1.22%)
    79 / 8028 (0.98%)
    12 / 3144 (0.38%)
    9 / 2309 (0.39%)
         occurrences causally related to treatment / all
    0 / 131
    0 / 108
    0 / 16
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chalazion
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Choroiditis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Corneal opacity
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystoid macular oedema
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dacryostenosis acquired
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Entropion
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Excessive eye blinking
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eyelid ptosis
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    8 / 8043 (0.10%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratitis interstitial
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratopathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacrimal disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lens disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular degeneration
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular fibrosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular hole
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Maculopathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myopia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neovascular age-related macular degeneration
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Optic atrophy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Optic ischaemic neuropathy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Posterior capsule opacification
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    3 / 3144 (0.10%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal artery embolism
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal degeneration
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    2 / 8043 (0.02%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal dystrophy
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal vein thrombosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinopathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trichiasis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Visual acuity reduced
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Corneal scar
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Flat anterior chamber of eye
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Open angle glaucoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ciliary body disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia obstructive
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    9 / 8043 (0.11%)
    9 / 8028 (0.11%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 9
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    7 / 8043 (0.09%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal inflammation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Barrett's oesophagus
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    7 / 8043 (0.09%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Change of bowel habit
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    8 / 8043 (0.10%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 6
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    5 / 8043 (0.06%)
    7 / 8028 (0.09%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis microscopic
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    9 / 8043 (0.11%)
    10 / 8028 (0.12%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 10
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    12 / 8043 (0.15%)
    8 / 8028 (0.10%)
    2 / 3144 (0.06%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 9
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    9 / 8043 (0.11%)
    9 / 8028 (0.11%)
    5 / 3144 (0.16%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 9
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis intestinal haemorrhagic
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    7 / 8043 (0.09%)
    3 / 8028 (0.04%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum oesophageal
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dolichocolon acquired
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal perforation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    5 / 8043 (0.06%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysbacteriosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocele
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecal incontinence
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 8043 (0.00%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral hernia
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal mass
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal prolapse
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral hernia incarcerated
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric antral vascular ectasia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Gastric ulcer
         subjects affected / exposed
    5 / 8043 (0.06%)
    7 / 8028 (0.09%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    19 / 8043 (0.24%)
    10 / 8028 (0.12%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 19
    1 / 11
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroduodenitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal angiodysplasia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    6 / 8043 (0.07%)
    7 / 8028 (0.09%)
    1 / 3144 (0.03%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal motility disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Gastrointestinal obstruction
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal ulcer haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    8 / 8043 (0.10%)
    10 / 8028 (0.12%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 10
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    11 / 8043 (0.14%)
    10 / 8028 (0.12%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 10
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal ulcer
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids thrombosed
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernial eventration
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    7 / 8043 (0.09%)
    7 / 8028 (0.09%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    7 / 8043 (0.09%)
    11 / 8028 (0.14%)
    1 / 3144 (0.03%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 11
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Intestinal mass
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    11 / 8043 (0.14%)
    11 / 8028 (0.14%)
    3 / 3144 (0.10%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 12
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Intestinal prolapse
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intussusception
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischiorectal hernia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    6 / 8043 (0.07%)
    10 / 8028 (0.12%)
    2 / 3144 (0.06%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 10
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar hernia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mallory-Weiss syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesenteric artery embolism
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal achalasia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal fistula
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal pain
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal hypomotility
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis ulcerative
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral pain
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic cyst
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic mass
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pancreatic pseudocyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    8 / 8043 (0.10%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    8 / 8043 (0.10%)
    5 / 8028 (0.06%)
    3 / 3144 (0.10%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    4 / 8043 (0.05%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    3 / 8043 (0.04%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer perforation
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngo-oesophageal diverticulum
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    6 / 8043 (0.07%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal prolapse
         subjects affected / exposed
    4 / 8043 (0.05%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salivary gland calculus
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    4 / 8043 (0.05%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic artery aneurysm
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomach mass
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis mesenteric vessel
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toothache
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    4 / 8043 (0.05%)
    10 / 8028 (0.12%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 10
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Varices oesophageal
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 8043 (0.04%)
    6 / 8028 (0.07%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    9 / 8043 (0.11%)
    3 / 8028 (0.04%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary fistula
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    20 / 8043 (0.25%)
    15 / 8028 (0.19%)
    3 / 3144 (0.10%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 15
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    7 / 8043 (0.09%)
    15 / 8028 (0.19%)
    1 / 3144 (0.03%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 15
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    34 / 8043 (0.42%)
    34 / 8028 (0.42%)
    7 / 3144 (0.22%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 34
    0 / 38
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic hepatitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder disorder
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder polyp
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    4 / 8043 (0.05%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Hepatic cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hepatic steatosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis cholestatic
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatorenal failure
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-alcoholic steatohepatitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Post cholecystectomy syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocholecystis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perforation bile duct
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute generalised exanthematous pustulosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angioedema
         subjects affected / exposed
    2 / 8043 (0.02%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrophoderma of Pasini and Pierini
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blister
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Dermal cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis allergic
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis contact
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis atopic
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatomyositis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eczema asteatotic
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema multiforme
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema nodosum
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand dermatitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Henoch-Schonlein purpura
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkeratosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity vasculitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ingrowing nail
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lentigo
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukoplakia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lichen sclerosus
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurodermatitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pemphigus
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pruritus generalised
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyoderma gangrenosum
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash erythematous
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash generalised
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    4 / 8043 (0.05%)
    6 / 8028 (0.07%)
    3 / 3144 (0.10%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Skin wrinkling
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    6 / 8043 (0.07%)
    6 / 8028 (0.07%)
    1 / 3144 (0.03%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Acute prerenal failure
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Bladder cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder diverticulum
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder irritation
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder perforation
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder prolapse
         subjects affected / exposed
    3 / 8043 (0.04%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus bladder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    1 / 8043 (0.01%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urethral
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    5 / 8043 (0.06%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis membranous
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis rapidly progressive
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    4 / 8043 (0.05%)
    5 / 8028 (0.06%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertonic bladder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    4 / 8043 (0.05%)
    10 / 8028 (0.12%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 10
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oliguria
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pollakiuria
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    2 / 8043 (0.02%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal mass
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal tubular disorder
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scleroderma renal crisis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress urinary incontinence
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral caruncle
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral polyp
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder polyp
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 8043 (0.01%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adrenal haemorrhage
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune thyroiditis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Goitre
         subjects affected / exposed
    2 / 8043 (0.02%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperadrenalism
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism primary
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Primary hypothyroidism
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Secondary hyperthyroidism
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroiditis subacute
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid mass
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 8043 (0.05%)
    6 / 8028 (0.07%)
    2 / 3144 (0.06%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    12 / 8043 (0.15%)
    8 / 8028 (0.10%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 10
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis reactive
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atlantoaxial instability
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Axillary mass
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    20 / 8043 (0.25%)
    22 / 8028 (0.27%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 22
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone loss
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    4 / 8043 (0.05%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondropathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Connective tissue disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dupuytren's contracture
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eosinophilic fasciitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facet joint syndrome
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    12 / 8043 (0.15%)
    10 / 8028 (0.12%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 11
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture delayed union
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture malunion
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture pain
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    12 / 8043 (0.15%)
    10 / 8028 (0.12%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 10
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc space narrowing
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaw cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint adhesion
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint contracture
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint stiffness
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint range of motion decreased
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint swelling
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Knee deformity
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    9 / 8043 (0.11%)
    6 / 8028 (0.07%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mobility decreased
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Monarthritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Morphoea
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    7 / 8043 (0.09%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nodal osteoarthritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    135 / 8043 (1.68%)
    115 / 8028 (1.43%)
    12 / 3144 (0.38%)
    12 / 2309 (0.52%)
         occurrences causally related to treatment / all
    0 / 154
    0 / 132
    0 / 12
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteochondritis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteosclerosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    9 / 8043 (0.11%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    2 / 10
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periarthritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periostitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plantar fasciitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    6 / 8043 (0.07%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    18 / 8043 (0.22%)
    11 / 8028 (0.14%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 12
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    5 / 8043 (0.06%)
    7 / 8028 (0.09%)
    4 / 3144 (0.13%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scoliosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sjogren's syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue necrosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    15 / 8043 (0.19%)
    17 / 8028 (0.21%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 17
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    3 / 8043 (0.04%)
    7 / 8028 (0.09%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondyloarthropathy
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    5 / 8043 (0.06%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    6 / 8043 (0.07%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tenosynovitis stenosans
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trigger finger
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulnocarpal abutment syndrome
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal sepsis
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Abdominal wall abscess
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amoebic colitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    18 / 8043 (0.22%)
    12 / 8028 (0.15%)
    6 / 3144 (0.19%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 12
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Beta haemolytic streptococcal infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    15 / 8043 (0.19%)
    14 / 8028 (0.17%)
    4 / 3144 (0.13%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 15
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    18 / 8043 (0.22%)
    17 / 8028 (0.21%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 18
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 7
    0 / 5
    0 / 0
    0 / 0
    Burn infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Campylobacter infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carbuncle
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    15 / 8043 (0.19%)
    16 / 8028 (0.20%)
    3 / 3144 (0.10%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 20
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Central nervous system viral infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chlamydial infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cutaneous tuberculosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    4 / 8043 (0.05%)
    8 / 8028 (0.10%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 8
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus gastrointestinal infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dacryocystitis
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    2 / 8043 (0.02%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dental fistula
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    25 / 8043 (0.31%)
    20 / 8028 (0.25%)
    4 / 3144 (0.13%)
    4 / 2309 (0.17%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 22
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Dysentery
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis infectious
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter pneumonia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    6 / 8043 (0.07%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema migrans
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder empyema
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Gastritis viral
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    34 / 8043 (0.42%)
    26 / 8028 (0.32%)
    1 / 3144 (0.03%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 34
    0 / 27
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis clostridial
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extradural abscess
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis intestinal haemorrhagic
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital candidiasis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Helicobacter gastritis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Helicobacter infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex encephalitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    5 / 8043 (0.06%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster infection neurological
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incision site infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Implant site infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected bites
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected dermal cyst
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected varicose vein
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    5 / 8043 (0.06%)
    7 / 8028 (0.09%)
    4 / 3144 (0.13%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal fistula infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratitis bacterial
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Labyrinthitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    11 / 8043 (0.14%)
    12 / 8028 (0.15%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 12
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    13 / 8043 (0.16%)
    9 / 8028 (0.11%)
    5 / 3144 (0.16%)
    2 / 2309 (0.09%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 9
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lyme disease
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    2 / 8043 (0.02%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaria
         subjects affected / exposed
    3 / 8043 (0.04%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mediastinitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Meningitis bacterial
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurosyphilis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic abscess
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parotitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic sepsis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    7 / 8043 (0.09%)
    5 / 8028 (0.06%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    117 / 8043 (1.45%)
    116 / 8028 (1.44%)
    31 / 3144 (0.99%)
    19 / 2309 (0.82%)
         occurrences causally related to treatment / all
    0 / 134
    0 / 121
    0 / 32
    0 / 19
         deaths causally related to treatment / all
    0 / 23
    0 / 23
    0 / 7
    0 / 3
    Pneumonia bacterial
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    2 / 8043 (0.02%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    3 / 8043 (0.04%)
    5 / 8028 (0.06%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal bacteraemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary echinococciasis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    3 / 8043 (0.04%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelocystitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    4 / 8043 (0.05%)
    7 / 8028 (0.09%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    5 / 8043 (0.06%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    3 / 8043 (0.04%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyometra
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyonephrosis
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salmonellosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    23 / 8043 (0.29%)
    18 / 8028 (0.22%)
    2 / 3144 (0.06%)
    5 / 2309 (0.22%)
         occurrences causally related to treatment / all
    0 / 24
    0 / 19
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 14
    0 / 10
    0 / 0
    0 / 3
    Septic shock
         subjects affected / exposed
    12 / 8043 (0.15%)
    7 / 8028 (0.09%)
    6 / 3144 (0.19%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 7
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 10
    0 / 5
    0 / 4
    0 / 1
    Sialoadenitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinobronchitis
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal skin infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stoma site abscess
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 8043 (0.00%)
    4 / 8028 (0.05%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdiaphragmatic abscess
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tick-borne fever
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 8043 (0.02%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    54 / 8043 (0.67%)
    49 / 8028 (0.61%)
    16 / 3144 (0.51%)
    9 / 2309 (0.39%)
         occurrences causally related to treatment / all
    1 / 58
    1 / 59
    1 / 16
    0 / 11
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection pseudomonal
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    4 / 8043 (0.05%)
    4 / 8028 (0.05%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral labyrinthitis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    2 / 8043 (0.02%)
    7 / 8028 (0.09%)
    2 / 3144 (0.06%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound sepsis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal abscess
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    13 / 8043 (0.16%)
    7 / 8028 (0.09%)
    2 / 3144 (0.06%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 7
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    5 / 8043 (0.06%)
    10 / 8028 (0.12%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 10
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    8 / 8043 (0.10%)
    9 / 8028 (0.11%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    4 / 8043 (0.05%)
    2 / 8028 (0.02%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 8043 (0.00%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    3 / 8043 (0.04%)
    2 / 8028 (0.02%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 8043 (0.01%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hyperosmolar state
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    8 / 8043 (0.10%)
    6 / 8028 (0.07%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    3 / 8043 (0.04%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    8 / 8043 (0.10%)
    14 / 8028 (0.17%)
    4 / 3144 (0.13%)
    3 / 2309 (0.13%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 15
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophagia
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    2 / 8043 (0.02%)
    1 / 8028 (0.01%)
    1 / 3144 (0.03%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 8043 (0.01%)
    0 / 8028 (0.00%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic disorder
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 8043 (0.00%)
    1 / 8028 (0.01%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    2 / 8043 (0.02%)
    3 / 8028 (0.04%)
    0 / 3144 (0.00%)
    1 / 2309 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Base Study + First Extension: Odanacatib 50 mg OW Base Study + First Extension: Placebo Second Extension: Odanacatib 50 mg OW Second Extension: Odanacatib 50 mg OW (Placebo)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5659 / 8043 (70.36%)
    5624 / 8028 (70.05%)
    311 / 3144 (9.89%)
    209 / 2309 (9.05%)
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    476 / 8043 (5.92%)
    499 / 8028 (6.22%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    761
    736
    0
    0
    Contusion
         subjects affected / exposed
    386 / 8043 (4.80%)
    422 / 8028 (5.26%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    500
    568
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1104 / 8043 (13.73%)
    1084 / 8028 (13.50%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    1263
    1278
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    492 / 8043 (6.12%)
    483 / 8028 (6.02%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    574
    565
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    477 / 8043 (5.93%)
    500 / 8028 (6.23%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    552
    583
    0
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    488 / 8043 (6.07%)
    492 / 8028 (6.13%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    638
    652
    0
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    492 / 8043 (6.12%)
    504 / 8028 (6.28%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    547
    552
    0
    0
    Diarrhoea
         subjects affected / exposed
    589 / 8043 (7.32%)
    504 / 8028 (6.28%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    726
    608
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    471 / 8043 (5.86%)
    466 / 8028 (5.80%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    553
    544
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1221 / 8043 (15.18%)
    1151 / 8028 (14.34%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    1588
    1533
    0
    0
    Back pain
         subjects affected / exposed
    1194 / 8043 (14.85%)
    1136 / 8028 (14.15%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    1473
    1394
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    518 / 8043 (6.44%)
    461 / 8028 (5.74%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    589
    537
    0
    0
    Pain in extremity
         subjects affected / exposed
    751 / 8043 (9.34%)
    671 / 8028 (8.36%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    923
    797
    0
    0
    Osteoarthritis
         subjects affected / exposed
    785 / 8043 (9.76%)
    741 / 8028 (9.23%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    980
    910
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    450 / 8043 (5.59%)
    459 / 8028 (5.72%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    591
    611
    0
    0
    Influenza
         subjects affected / exposed
    495 / 8043 (6.15%)
    443 / 8028 (5.52%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    610
    564
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    957 / 8043 (11.90%)
    938 / 8028 (11.68%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    1396
    1365
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    644 / 8043 (8.01%)
    596 / 8028 (7.42%)
    0 / 3144 (0.00%)
    0 / 2309 (0.00%)
         occurrences all number
    962
    913
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1724 / 8043 (21.43%)
    1699 / 8028 (21.16%)
    311 / 3144 (9.89%)
    209 / 2309 (9.05%)
         occurrences all number
    2911
    2821
    393
    271

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Aug 2008
    Amendment 1; applicable to MK-0822-018 Base Study.
    06 Aug 2009
    Amendment 1: applicable to MK-0822-032 Imaging Substudy-Base
    14 Sep 2009
    Amendment 1: applicable to MK-0822-035 Imaging Substudy
    27 Apr 2010
    Amendment 2: applicable to MK-0822-018 Base Study.
    25 Apr 2011
    Amendment 10: defined Extension 1 to MK-0822-018 Base Study.
    11 Oct 2011
    Amendment 3: applicable to MK-0822-018 Base Study.
    11 Oct 2011
    Amendment 10: defined Extension to MK-0822-032 Imaging Substudy-Base.
    07 Mar 2012
    Amendment 4: applicable to MK-0822-018 Base Study.
    08 Jan 2013
    Amendment 5: applicable to MK-0822-018 Base Study.
    09 Jan 2013
    Amendment 20: defined Extension 2 to MK-0822-018 Base + Extension 1 Study.
    24 Jun 2013
    Amendment 6: applicable to MK-0822-018 Base Study.
    22 Nov 2013
    Amendment 11: applicable to MK-0822-032 Imaging Substudy-Extension.
    22 Jul 2014
    Amendment 21: applicable to MK-0822-018 Extension 2 Study.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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