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    Clinical Trial Results:
    A Multicenter, International, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis

    Summary
    EudraCT number
    		 2011-001456-11
    Trial protocol
    		 HU   BE   DK   PL   DE   GB   EE   CZ   ES   LV   LT  
    Global end of trial date
    28 Dec 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Jan 2018
    First version publication date
    03 Jan 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20070337
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01575834
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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
    28 Dec 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Dec 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to determine if treatment with romosozumab is effective in preventing fractures in women with postmenopausal osteoporosis
    Protection of trial subjects
    This study was conducted in accordance with applicable local, Food and Drug Administration, and International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. The study protocol, subject information, and informed consent form were reviewed and approved by the independent ethics committee (IEC) or institutional review board (IRB) for each study center. All subjects provided written informed consent before any protocol-specific screening procedures or any investigational products were administered and after the aims, methods, anticipated benefits, and potential hazards of the study were adequately explained.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Mar 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 61
    Country: Number of subjects enrolled
    Switzerland: 34
    Country: Number of subjects enrolled
    United Kingdom: 398
    Country: Number of subjects enrolled
    United States: 132
    Country: Number of subjects enrolled
    Argentina: 177
    Country: Number of subjects enrolled
    Australia: 25
    Country: Number of subjects enrolled
    Belgium: 26
    Country: Number of subjects enrolled
    Brazil: 816
    Country: Number of subjects enrolled
    Canada: 63
    Country: Number of subjects enrolled
    Colombia: 1822
    Country: Number of subjects enrolled
    Czech Republic: 334
    Country: Number of subjects enrolled
    Denmark: 334
    Country: Number of subjects enrolled
    Dominican Republic: 173
    Country: Number of subjects enrolled
    Estonia: 110
    Country: Number of subjects enrolled
    Germany: 67
    Country: Number of subjects enrolled
    Hong Kong: 231
    Country: Number of subjects enrolled
    Hungary: 203
    Country: Number of subjects enrolled
    India: 106
    Country: Number of subjects enrolled
    Japan: 492
    Country: Number of subjects enrolled
    Latvia: 51
    Country: Number of subjects enrolled
    Lithuania: 112
    Country: Number of subjects enrolled
    Mexico: 96
    Country: Number of subjects enrolled
    New Zealand: 34
    Country: Number of subjects enrolled
    Poland: 1241
    Country: Number of subjects enrolled
    Romania: 42
    Worldwide total number of subjects
    7180
    EEA total number of subjects
    2979
    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)
    1525
    From 65 to 84 years
    5439
    85 years and over
    216

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 222 centers in Europe, Central/Latin America, Asia, North America, and Australia/New Zealand. The first participant enrolled on 15 March 2012 and the last participant enrolled on 06 December 2013.

    Pre-assignment
    Screening details
    		 Participants were randomized 1:1 to receive either romosozumab 210 mg or matched placebo for the 12-month, double-blind, placebo-controlled period. Randomization was stratified by age (< 75 years, ≥ 75 years) and prevalent vertebral fracture (yes, no), as determined by site staff at randomization based on local reading of the spine X-ray.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Denosumab
    Arm description
    		 Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once a month

    Investigational medicinal product name
    Denosumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 6 months

    Arm title
    		 Romosozumab/Denosumab
    Arm description
    		 Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Denosumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 6 months

    Investigational medicinal product name
    Romosozumab
    Investigational medicinal product code
    AMG 785
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once a month

    Number of subjects in period 1
    		Placebo/Denosumab Romosozumab/Denosumab
    Started
    3591
    3589
    Received Double-blind Treatment
    3582
    3575
    Completed Double-blind Period
    3205
    3185
    Completed 24-month Study Period
    3032
    2994
    Completed
    2892
    2851
    Not completed
    699
    738
         Consent withdrawn by subject
    352
    390
         Adverse event, non-fatal
    63
    61
         Administrative decision
    15
    33
         Death
    81
    74
         Other
    70
    70
         Protocol deviation
    4
    3
         Lost to follow-up
    55
    68
         Ineligibility determined
    5
    8
         Noncompliance
    52
    27
         Requirement for alternative therapy
    2
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo/Denosumab
    Reporting group description
    		 Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group title
    Romosozumab/Denosumab
    Reporting group description
    		 Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group values
    		 Placebo/Denosumab Romosozumab/Denosumab Total
    Number of subjects
    		 3591 3589 7180
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    		 757 768 1525
        From 65-84 years
    		 2727 2712 5439
        85 years and over
    		 107 109 216
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 70.8 ( 6.9 ) 70.9 ( 7.0 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 3591 3589 7180
        Male
    		 0 0 0
    Race
    Units: Subjects
        White
    		 2052 2063 4115
        Asian
    		 441 425 866
        Black or African American
    		 74 77 151
        American Indian/Alaska Native
    		 63 64 127
        Native Hawaiian/Other Pacific Islander
    		 1 0 1
        Multiple
    		 59 60 119
        Other
    		 901 900 1801
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1416 1427 2843
        Not Hispanic or Latino
    		 2175 2162 4337
    Prevalent Vertebral Fracture Strata per Randomization
    Strata per randomization for prevalent fracture were based on local reading of baseline spine radiographs.
    Units: Subjects
        Yes
    		 205 204 409
        No
    		 3386 3385 6771
    Age Strata per Randomization
    Units: Subjects
        < 75 years
    		 2471 2470 4941
        ≥ 75 years
    		 1120 1119 2239

    End points

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    End points reporting groups
    Reporting group title
    Placebo/Denosumab
    Reporting group description
    		 Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group title
    Romosozumab/Denosumab
    Reporting group description
    		 Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Primary: Percentage of Participants with New Vertebral Fracture Through Month 12

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    End point title
    		 Percentage of Participants with New Vertebral Fracture Through Month 12
    End point description
    New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: • Grade 0 (Normal) = no fracture; • Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); • Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; • Grade 3 (Severe) = severe fracture, > 40% reduction in anterior, middle, and/or posterior height. The primary analysis set for vertebral fractures includes all subjects with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 12 months, including subjects with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
    End point type
    Primary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3322
    3321
    Units: percentage of participants
        number (not applicable)
    1.8
    0.5
    Statistical analysis title
    		 Analysis of New Vertebral Fracture To Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6643
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.001 [2]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.15
         upper limit
    		 0.47
    Notes
    [1] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [2] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Primary: Percentage of Participants with New Vertebral Fracture Through Month 24

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    End point title
    		 Percentage of Participants with New Vertebral Fracture Through Month 24
    End point description
    New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: • Grade 0 (Normal) = no fracture; • Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); • Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; • Grade 3 (Severe) = severe fracture, > 40% reduction in anterior, middle, and/or posterior height. The primary analysis set for vertebral fractures includes all subjects with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 24 months, including subjects with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
    End point type
    Primary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3327
    3325
    Units: percentage of participants
        number (not applicable)
    2.5
    0.6
    Statistical analysis title
    		 Analysis of New Vertebral Fracture To Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6652
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.001 [4]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.15
         upper limit
    		 0.39
    Notes
    [3] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [4] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percentage of Participants with a Clinical Fracture Through Month 12

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    End point title
    		 Percentage of Participants with a Clinical Fracture Through Month 12
    End point description
    Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set consisted of all randomized participants. Last observation carried forward imputation (LOCF) was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    2.5
    1.6
    Statistical analysis title
    		 Analysis of Clinical Fracture Through Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.008 [6]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 0.89
    Notes
    [5] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [6] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Nonvertebral Fracture Through Month 12

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    End point title
    		 Percentage of Participants with a Nonvertebral Fracture Through Month 12
    End point description
    A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    2.1
    1.6
    Statistical analysis title
    		 Analysis of Nonvertebral Fracture Through Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.096 [8]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.05
    Notes
    [7] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [8] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Nonvertebral Fracture Through Month 24

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    End point title
    		 Percentage of Participants with a Nonvertebral Fracture Through Month 24
    End point description
    A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date as recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set was used for the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    3.6
    2.7
    Statistical analysis title
    		 Analysis of Nonvertebral Fracture Through Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.057 [10]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 0.97
    Notes
    [9] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [10] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Clinical Fracture Through Month 24

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    End point title
    		 Percentage of Participants with a Clinical Fracture Through Month 24
    End point description
    Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set with LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    4.1
    2.8
    Statistical analysis title
    		 Analysis of Clinical Fracture Through Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.096 [12]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 0.87
    Notes
    [11] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [12] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Nonvertebral Fracture Through Month 12

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    End point title
    		 Percentage of Participants with a Major Nonvertebral Fracture Through Month 12
    End point description
    A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip. The full analysis set was used for the analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    1.5
    1.0
    Statistical analysis title
    		 Analysis of Major Nonvertebral Fracture
    Statistical analysis description
    Analysis of major nonvertebral fracture through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.096 [14]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 1.02
    Notes
    [13] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [14] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Nonvertebral Fracture Through Month 24

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    End point title
    		 Percentage of Participants with a Major Nonvertebral Fracture Through Month 24
    End point description
    A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip. The full analysis set was used for the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    2.8
    1.9
    Statistical analysis title
    		 Analysis of Major Nonvertebral Fracture
    Statistical analysis description
    Analysis of major nonvertebral fracture through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 = 0.096 [16]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 0.91
    Notes
    [15] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [16] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 12

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    End point title
    		 Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 12
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. The primary analysis set for vertebral fractures with LOCF imputation was used for the analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3322
    3321
    Units: percentage of participants
        number (not applicable)
    1.8
    0.5
    Statistical analysis title
    		 Analysis of New or Worsening Vertebral Fracture
    Statistical analysis description
    Analysis of new or worsening vertebral fracture through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6643
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.096 [18]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.17
         upper limit
    		 0.49
    Notes
    [17] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [18] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 24

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    End point title
    		 Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 24
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. The primary analysis set for vertebral fractures with LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3327
    3325
    Units: percentage of participants
        number (not applicable)
    2.5
    0.7
    Statistical analysis title
    		 Analysis of New or Worsening Vertebral Fracture
    Statistical analysis description
    Analysis of new or worsening vertebral fracture through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6652
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    P-value
    		 = 0.096 [20]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 0.41
    Notes
    [19] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [20] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test

    Secondary: Percentage of Participants with a Hip Fracture Through Month 12

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    End point title
    		 Percentage of Participants with a Hip Fracture Through Month 12
    End point description
    Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    0.4
    0.2
    Statistical analysis title
    		 Analysis of Hip Fracture Through Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    P-value
    		 = 0.18 [22]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 1.35
    Notes
    [21] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [22] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Hip Fracture Through Month 24

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    End point title
    		 Percentage of Participants with a Hip Fracture Through Month 24
    End point description
    Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    0.6
    0.3
    Statistical analysis title
    		 Analysis of Hip Fracture Through Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 = 0.12 [24]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 1.04
    Notes
    [23] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [24] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Osteoporotic Fracture Through Month 12

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    End point title
    		 Percentage of Participants with a Major Osteoporotic Fracture Through Month 12
    End point description
    Major osteoporotic fractures included hip, forearm, or humerus fractures that were not associated with a pathologic fracture regardless of trauma severity, and clinical vertebral fractures. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    1.8
    1.1
    Statistical analysis title
    		 Analysis of Major Osteoporotic Fracture
    Statistical analysis description
    Analysis of major osteoporotic fracture through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.012 [25]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 0.9
    Notes
    [25] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Osteoporotic Fracture Through Month 24

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    End point title
    		 Percentage of Participants with a Major Osteoporotic Fracture Through Month 24
    End point description
    Major osteoporotic fractures included hip, forearm, or humerus fractures that were not associated with a pathologic fracture regardless of trauma severity, and clinical vertebral fractures. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    3.1
    1.9
    Statistical analysis title
    		 Analysis of Major Osteoporotic Fracture
    Statistical analysis description
    Analysis of major osteoporotic fracture through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002 [26]
    Method
    		 Cox proportional hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 0.84
    Notes
    [26] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 12

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    End point title
    		 Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 12
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit. The primary analysis set for vertebral fractures with LOCF imputation was used for the analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3322
    3321
    Units: percentage of participants
        number (not applicable)
    0.3
    0.03
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Analysis of multiple new or worsening vertebral fractures through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6643
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011 [27]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.87
    Notes
    [27] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 24

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    End point title
    		 Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 24
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit. The primary analysis set for vertebral fractures with LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3327
    3325
    Units: percentage of participants
        number (not applicable)
    0.5
    0.03
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Analysis of multiple new or worsening vertebral fractures through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6652
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [28]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.44
    Notes
    [28] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Lumbar Spine at Month 12

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    End point title
    		 Percent Change from Baseline in Bone Mineral Density at the Lumbar Spine at Month 12
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and month 12
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3148
    3151
    Units: percent change
        least squares mean (standard error)
    0.4 ( 0.1 )
    13.1 ( 0.1 )
    Statistical analysis title
    		 Analysis of Lumbar Spine BMD at Month 12
    Statistical analysis description
    The treatment comparison of BMD at the lumbar spine was analyzed using an analysis of covariance (ANCOVA) model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6299
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    12.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.4
         upper limit
    		 12.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline In Bone Mineral Density at the Lumbar Spine at Month 24

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    End point title
    		 Percent Change from Baseline In Bone Mineral Density at the Lumbar Spine at Month 24
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Month 24
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    2877
    2861
    Units: percent change
        least squares mean (standard error)
    5.5 ( 0.1 )
    16.6 ( 0.1 )
    Statistical analysis title
    		 Analysis of Lumbar Spine BMD at Month 24
    Statistical analysis description
    The treatment comparison of BMD at the lumbar spine was analyzed using an analysis of covariance (ANCOVA) model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    5738
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    11.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.8
         upper limit
    		 11.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 12

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    End point title
    		 Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 12
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and month 12
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3210
    3197
    Units: percent change
        least squares mean (standard error)
    0.3 ( 0.1 )
    6.0 ( 0.1 )
    Statistical analysis title
    		 Analysis of Total Hip BMD at Month 12
    Statistical analysis description
    The treatment comparison of BMD at the total hip was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6407
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    5.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.6
         upper limit
    		 6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 24

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    End point title
    		 Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 24
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and month 24
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    2918
    2903
    Units: percent change
        least squares mean (standard error)
    3.2 ( 0.1 )
    8.5 ( 0.1 )
    Statistical analysis title
    		 Analysis of Total Hip BMD at Month 24
    Statistical analysis description
    The treatment comparison of BMD at the total hip was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    5821
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    5.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.1
         upper limit
    		 5.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 12

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    End point title
    		 Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 12
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and month 12
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3210
    3197
    Units: percent change
        least squares mean (standard error)
    0.3 ( 0.1 )
    5.5 ( 0.1 )
    Statistical analysis title
    		 Analysis of Femoral Neck BMD at Month 12
    Statistical analysis description
    The treatment comparison of BMD at the femoral neck was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6407
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.9
         upper limit
    		 5.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 24

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    End point title
    		 Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 24
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and month 24
    End point values
    		 Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    2918
    2903
    Units: percent change
        least squares mean (standard error)
    2.3 ( 0.1 )
    7.3 ( 0.1 )
    Statistical analysis title
    		 Analysis of Femoral Neck BMD at Month 24
    Statistical analysis description
    The treatment comparison of BMD at the femoral neck was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    5821
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    4.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.7
         upper limit
    		 5.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Double-blind treatment period: 12 months; Overall study: 36 months
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    12-Month Double-blind Period: Placebo
    Reporting group description
    		 Participants received placebo subcutaneous injections once a month for 12 months.

    Reporting group title
    12-Month Double-blind Period: Romosozumab
    Reporting group description
    		 Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months.

    Reporting group title
    36-Month Study Period: Placebo/Denosumab
    Reporting group description
    		 Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group title
    36-Month Study Period: Romosozumab/Denosumab
    Reporting group description
    		 Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Serious adverse events
    		 12-Month Double-blind Period: Placebo 12-Month Double-blind Period: Romosozumab 36-Month Study Period: Placebo/Denosumab 36-Month Study Period: Romosozumab/Denosumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    314 / 3576 (8.78%)
    344 / 3581 (9.61%)
    733 / 3576 (20.50%)
    728 / 3581 (20.33%)
         number of deaths (all causes)
    24
    29
    85
    72
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acral lentiginous melanoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Adenocarcinoma gastric
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    8 / 3576 (0.22%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
    0 / 1
    Adenocarcinoma of colon
         subjects affected / exposed
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Adrenal adenoma
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adrenal neoplasm
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Anal cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Angiocentric lymphoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Basal cell carcinoma
         subjects affected / exposed
    5 / 3576 (0.14%)
    2 / 3581 (0.06%)
    6 / 3576 (0.17%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basosquamous carcinoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Benign breast neoplasm
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Benign gastric neoplasm
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Benign neoplasm of adrenal gland
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Benign neoplasm of bladder
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of spinal cord
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Benign ovarian tumour
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Benign pleural neoplasm
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Benign salivary gland neoplasm
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Benign soft tissue neoplasm
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Bladder cancer
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Bowen's disease
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Brain neoplasm malignant
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Breast cancer
         subjects affected / exposed
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
    11 / 3576 (0.31%)
    8 / 3581 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 12
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Breast cancer female
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer in situ
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Breast cancer recurrent
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Breast cancer stage II
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Breast cancer stage III
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Bronchial carcinoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Cervix carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cervix carcinoma stage II
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Choroid melanoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Colon adenoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Colon neoplasm
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Colorectal adenocarcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Colorectal cancer
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Endometrial adenocarcinoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Fibrous histiocytoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Gallbladder cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Gastric cancer
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Granular cell tumour
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Haemangioma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Hepatic cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Intraocular melanoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
    1 / 3576 (0.03%)
    4 / 3581 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine benign neoplasm
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lentigo maligna
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma metastatic
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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 / 1
    Lung neoplasm malignant
         subjects affected / exposed
    6 / 3576 (0.17%)
    7 / 3581 (0.20%)
    10 / 3576 (0.28%)
    13 / 3581 (0.36%)
         occurrences causally related to treatment / all
    2 / 7
    0 / 7
    2 / 13
    2 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
    1 / 6
    Lymphoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Malignant neoplasm of conjunctiva
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Mantle cell lymphoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Meningioma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Meningioma benign
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Metastases to liver
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Metastases to pleura
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Metastatic bronchial carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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 malignant melanoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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 / 1
    Nasopharyngeal cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Neoplasm of appendix
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Neuroendocrine carcinoma of the skin
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Neurofibroma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Oesophageal squamous cell carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Oesophageal squamous cell carcinoma recurrent
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Ovarian adenoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    3 / 3576 (0.08%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    Ovarian cancer metastatic
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Paget's disease of nipple
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Pancoast's tumour
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic neuroendocrine tumour
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Paranasal sinus benign neoplasm
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Phaeochromocytoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Pituitary tumour benign
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Plasma cell myeloma
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyogenic granuloma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Rectal cancer
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         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
    Rectal cancer stage II
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectosigmoid cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Renal adenoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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 cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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 cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Small cell lung cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestine adenocarcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Small intestine carcinoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Squamous cell carcinoma
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Squamous cell carcinoma of pharynx
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the hypopharynx
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Tracheal cancer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Uterine leiomyoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         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
    Aortic thrombosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Arterial occlusive disease
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Arterial stenosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Arteriosclerosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Circulatory collapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    Deep vein thrombosis
         subjects affected / exposed
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
    3 / 3576 (0.08%)
    5 / 3581 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    Dry gangrene
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Extremity necrosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Hypertension
         subjects affected / exposed
    5 / 3576 (0.14%)
    8 / 3581 (0.22%)
    12 / 3576 (0.34%)
    15 / 3581 (0.42%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
    0 / 14
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    2 / 3576 (0.06%)
    6 / 3581 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Hypotension
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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 artery stenosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Shock haemorrhagic
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Thrombophlebitis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Varicose ulceration
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         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
    Varicose vein
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular insufficiency
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Vasculitis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Venous thrombosis limb
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Surgical and medical procedures
    Cardiac pacemaker replacement
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Cataract operation
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Hysterectomy
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Knee arthroplasty
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Osteosynthesis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Pulmonary resection
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Rehabilitation therapy
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Scar excision
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Chest pain
         subjects affected / exposed
    1 / 3576 (0.03%)
    3 / 3581 (0.08%)
    3 / 3576 (0.08%)
    4 / 3581 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Death
         subjects affected / exposed
    5 / 3576 (0.14%)
    5 / 3581 (0.14%)
    9 / 3576 (0.25%)
    13 / 3581 (0.36%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 9
    1 / 13
         deaths causally related to treatment / all
    0 / 5
    0 / 5
    0 / 9
    1 / 13
    General physical health deterioration
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Malaise
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Medical device discomfort
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Mucosal dryness
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    3 / 3576 (0.08%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 3576 (0.00%)
    4 / 3581 (0.11%)
    3 / 3576 (0.08%)
    10 / 3581 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
    0 / 3
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Sudden death
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 4
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Drug hypersensitivity
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Hypersensitivity
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Activities of daily living impaired
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Immobile
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical polyp
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Cystocele
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Endometrial hypertrophy
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Female genital tract fistula
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibrocystic breast disease
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Ovarian cyst
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Pelvic haematoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Pelvic prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Rectocele
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Urogenital prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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 polyp
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    5 / 3581 (0.14%)
    2 / 3576 (0.06%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterovaginal prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal haematoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Vaginal polyp
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Vaginal prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Alveolitis allergic
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Asthma
         subjects affected / exposed
    2 / 3576 (0.06%)
    3 / 3581 (0.08%)
    3 / 3576 (0.08%)
    8 / 3581 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Bronchiectasis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Choking sensation
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    15 / 3576 (0.42%)
    6 / 3581 (0.17%)
    28 / 3576 (0.78%)
    22 / 3581 (0.61%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 6
    0 / 35
    1 / 24
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    Dyspnoea exertional
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Epistaxis
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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 / 1
    Pneumothorax
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    6 / 3576 (0.17%)
    9 / 3581 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    Pulmonary mass
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Respiratory distress
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Respiratory failure
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    Sinus polyp
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Vocal cord cyst
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Alcoholism
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Anxiety disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Bipolar I disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Bipolar disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Delirium
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    4 / 3576 (0.11%)
    1 / 3581 (0.03%)
    6 / 3576 (0.17%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         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
    Major depression
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Mental status changes
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Personality change due to a general medical condition
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Pseudodementia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Psychotic disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Schizophreniform disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Suicide attempt
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Transient psychosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Bile duct stone
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Biliary colic
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary dilatation
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Cholangitis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Cholangitis sclerosing
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Cholecystitis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 3576 (0.03%)
    3 / 3581 (0.08%)
    6 / 3576 (0.17%)
    5 / 3581 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    8 / 3576 (0.22%)
    5 / 3581 (0.14%)
    11 / 3576 (0.31%)
    12 / 3581 (0.34%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
    0 / 11
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis obstructive
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Cholestasis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cyst
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Hepatic failure
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Hepatic steatosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Hepatocellular injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic hepatitis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Jaundice
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Jaundice cholestatic
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Liver disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Liver injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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 hypertension
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Portal vein thrombosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Sphincter of Oddi dysfunction
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Investigations
    Blood lactic acid increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Blood pressure decreased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Blood pressure increased
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         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
    Body mass index increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Gastric pH decreased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    General physical condition abnormal
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Haemoglobin decreased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Influenza B virus test positive
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Liver function test increased
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 2
    1 / 2
         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
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Accidental overdose
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Acetabulum fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Brain contusion
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Cataract operation complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Concussion
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    Eye injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Eyelid injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Face injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Facial bones fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Fall
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    6 / 3576 (0.17%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    8 / 3576 (0.22%)
    3 / 3581 (0.08%)
    14 / 3576 (0.39%)
    11 / 3581 (0.31%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
    0 / 14
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    7 / 3576 (0.20%)
    4 / 3581 (0.11%)
    19 / 3576 (0.53%)
    9 / 3581 (0.25%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    0 / 19
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    4 / 3576 (0.11%)
    4 / 3581 (0.11%)
    8 / 3576 (0.22%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Fractured sacrum
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Gastrointestinal stoma complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Hand fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Head injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
    3 / 3576 (0.08%)
    6 / 3581 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    8 / 3576 (0.22%)
    8 / 3581 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Internal injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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 dislocation
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         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
    Joint injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Ligament sprain
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Limb injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Muscle rupture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Muscle strain
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Overdose
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Patella fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Post concussion syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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 complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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 haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Postoperative adhesion
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative delirium
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (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
    Procedural complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Procedural hypotension
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Procedural pain
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Pubis fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radial head dislocation
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         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
    Radius fracture
         subjects affected / exposed
    5 / 3576 (0.14%)
    3 / 3581 (0.08%)
    17 / 3576 (0.48%)
    14 / 3581 (0.39%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 17
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (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
    Spinal fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    3 / 3576 (0.08%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0