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    Clinical Trial Results:
    A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects with Early Alzheimer's Disease

    Summary
    EudraCT number
    2015-000966-72
    Trial protocol
    IT   DE   AT   FR   PT   ES   DK   GB  
    Global end of trial date
    08 Aug 2019

    Results information
    Results version number
    v2(current)
    This version publication date
    06 Oct 2021
    First version publication date
    20 Nov 2020
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    221AD301
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02477800
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Biogen
    Sponsor organisation address
    250 Binney Street, Cambridge, United States, 02142
    Public contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
    Scientific contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.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
    08 Aug 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Aug 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in subjects with early Alzheimer's Disease (AD).
    Protection of trial subjects
    Written informed consent was obtained from each subject or subject’s legally authorized representative (e.g., legal guardian), as applicable, prior to evaluations performed for eligibility. Subjects or the subject’s legally authorized representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    13 Aug 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy, Safety
    Long term follow-up duration
    4 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 102
    Country: Number of subjects enrolled
    Canada: 84
    Country: Number of subjects enrolled
    Japan: 100
    Country: Number of subjects enrolled
    Korea, Republic of: 50
    Country: Number of subjects enrolled
    Taiwan: 13
    Country: Number of subjects enrolled
    United States: 766
    Country: Number of subjects enrolled
    Austria: 9
    Country: Number of subjects enrolled
    Denmark: 23
    Country: Number of subjects enrolled
    France: 60
    Country: Number of subjects enrolled
    Germany: 97
    Country: Number of subjects enrolled
    Italy: 116
    Country: Number of subjects enrolled
    Portugal: 47
    Country: Number of subjects enrolled
    Spain: 105
    Country: Number of subjects enrolled
    United Kingdom: 81
    Worldwide total number of subjects
    1653
    EEA total number of subjects
    457
    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)
    371
    From 65 to 84 years
    1272
    85 years and over
    10

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects were enrolled at 169 investigational sites in Australia, Austria, Canada, Denmark, France, Germany, Italy, Japan, Portugal, Republic of Korea, Spain, Taiwan, the United Kingdom (UK) and the United States (US) from 13 August, 2015 to 04 July, 2018.

    Pre-assignment
    Screening details
    A total of 1653 subjects with Alzheimer's disease were enrolled and randomised in the study. Of these, 1647 subjects received the study drug in placebo-controlled (PC) period. After completing PC period, 852 subjects entered and dosed in long-term extension (LTE) period and no subjects completed the study due to early termination of the study.

    Period 1
    Period 1 title
    Placebo-Controlled Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Monitor, Subject, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo (PC Period)
    Arm description
    Subjects received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion, once every 4 weeks.

    Arm title
    BIIB037 Low Dose (PC Period)
    Arm description
    Subjects received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB037
    Investigational medicinal product code
    Other name
    Aducanumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion, once every 4 weeks.

    Arm title
    BIIB037 High Dose (PC Period)
    Arm description
    Subjects received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB037
    Investigational medicinal product code
    Other name
    Aducanumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion, once every 4 weeks.

    Number of subjects in period 1 [1]
    Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
    Started
    545
    547
    555
    Completed
    325
    325
    288
    Not completed
    220
    222
    267
         Disease Progression
    1
    -
    1
         Death
    -
    3
    2
         Change of Treatment
    1
    2
    1
         Investigator Decision
    3
    2
    1
         Withdrawal by Parent/Guardian
    1
    5
    3
         Relocation
    2
    -
    -
         Reason not Specified
    161
    161
    189
         Site Terminated By Sponsor
    2
    1
    -
         Consent Withdrawn
    26
    16
    27
         Study Visit Burden
    5
    3
    11
         Site Terminated by Investigator
    1
    1
    1
         Adverse Event
    16
    25
    28
         Lost to follow-up
    1
    3
    3
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of subjects reported in the baseline period is for intent to treat population (545 subjects in placebo arm, 547 subjects in BIIB037 Low Dose arm, 555 subjects in BIIB037 High Dose arm).
    Period 2
    Period 2 title
    Long Term Extension Period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    BIIB037 Late Start: Low Dose (LTE Period)
    Arm description
    Following PC period, subjects randomized to placebo received BIIB037 low dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB037
    Investigational medicinal product code
    Other name
    Aducanumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion, once every 4 weeks.

    Arm title
    BIIB037 Late Start: High Dose (LTE Period)
    Arm description
    Following PC period, subjects randomized to placebo received BIIB037 high dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB037
    Investigational medicinal product code
    Other name
    Aducanumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion, once every 4 weeks.

    Arm title
    BIIB037 Early Start: Low Dose (LTE Period)
    Arm description
    Following PC period, subjects randomized to low dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB037
    Investigational medicinal product code
    Other name
    Aducanumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion, once every 4 weeks.

    Arm title
    BIIB037 Early Start: High Dose (LTE Period)
    Arm description
    Following PC period, subjects randomized to high dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB037
    Investigational medicinal product code
    Other name
    Aducanumab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion, once every 4 weeks.

    Number of subjects in period 2 [2]
    BIIB037 Late Start: Low Dose (LTE Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period)
    Started
    150
    152
    299
    251
    Completed
    0
    0
    0
    0
    Not completed
    150
    152
    299
    251
         Site Terminated By Sponsor
    -
    -
    2
    1
         Death
    1
    1
    1
    2
         Disease Progression
    3
    1
    1
    -
         Consent Withdrawn
    10
    4
    13
    16
         Study Visit Burden
    3
    -
    2
    2
         Investigator Decision
    -
    -
    -
    2
         Withdrawal by Parent/Guardian
    1
    3
    3
    1
         Reason not Specified
    126
    140
    270
    224
         Adverse Event
    6
    2
    4
    3
         Lost to follow-up
    -
    1
    3
    -
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 938 subjects completed the PC period, out of which only 852 subjects entered in LTE period. 86 subjects from PC period did not enter LTE period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo (PC Period)
    Reporting group description
    Subjects received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.

    Reporting group title
    BIIB037 Low Dose (PC Period)
    Reporting group description
    Subjects received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.

    Reporting group title
    BIIB037 High Dose (PC Period)
    Reporting group description
    Subjects received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.

    Reporting group values
    Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) Total
    Number of subjects
    545 547 555
    Age categorical
    Units: subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    69.8 ± 7.72 70.4 ± 6.96 70.0 ± 7.65 -
    Sex: Female, Male
    Units: subjects
        Female
    287 284 292 863
        Male
    258 263 263 784
    Race
    Units: Subjects
        Asian
    55 55 65 175
        Black or African American
    5 1 2 8
        Native Hawaiian or other Pacific Islander
    0 1 0 1
        White
    413 412 413 1238
        Not reported due to confidentiality regulations
    69 74 72 215
        Other
    3 4 3 10
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    13 11 13 37
        Not Hispanic or Latino
    489 492 499 1480
        Not reported due to confidentiality regulations
    43 44 43 130

    End points

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    End points reporting groups
    Reporting group title
    Placebo (PC Period)
    Reporting group description
    Subjects received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.

    Reporting group title
    BIIB037 Low Dose (PC Period)
    Reporting group description
    Subjects received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.

    Reporting group title
    BIIB037 High Dose (PC Period)
    Reporting group description
    Subjects received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
    Reporting group title
    BIIB037 Late Start: Low Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to placebo received BIIB037 low dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Reporting group title
    BIIB037 Late Start: High Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to placebo received BIIB037 high dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Reporting group title
    BIIB037 Early Start: Low Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to low dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Reporting group title
    BIIB037 Early Start: High Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to high dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Primary: Change from Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score at Week 78

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    End point title
    Change from Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score at Week 78
    End point description
    CDR-SB integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic patient examination, the rater assigns a score describing the subject’s current performance level in each of these domains of life functioning. Prespecified severity anchors range from none = 0, questionable = 0.5, mild = 1, moderate = 2 to severe = 3 (the personal care domain omits the 0.5 score). “Sum of boxes” scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18 that can change in increments of 0.5 or greater. Higher scores indicate greater disease severity. Mixed model for repeated measures (MMRM) analysis was used to analyse change from baseline in CDR-SB. A positive change from baseline indicates clinical decline. Intent-to-Treat (ITT) population. n=number of subjects analysed at specific timepoint.
    End point type
    Primary
    End point timeframe
    Baseline, Week 78
    End point values
    Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
    Number of subjects analysed
    545
    547
    555
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n =333,331,295)
    1.56 ± 0.108
    1.38 ± 0.108
    1.59 ± 0.111
    Statistical analysis title
    Placebo vs BIIB037 Low Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in CDR-SB as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline CDR-SB, baseline CDR-SB by visit interaction, baseline MMSE, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 Low Dose (PC Period)
    Number of subjects included in analysis
    1092
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.225
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    -0.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.469
         upper limit
    0.11
    Statistical analysis title
    Placebo vs BIIB037 High Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in CDR-SB as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline CDR-SB, baseline CDR-SB by visit interaction, baseline MMSE, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 High Dose (PC Period)
    Number of subjects included in analysis
    1100
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.833
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.262
         upper limit
    0.326

    Secondary: Change from Baseline in Mini-Mental State Examination (MMSE) Score at Week 78

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    End point title
    Change from Baseline in Mini-Mental State Examination (MMSE) Score at Week 78
    End point description
    The MMSE is a widely used performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30, with lower scores over time indicating increasing cognitive impairment. MMRM analysis was used to analyse change from baseline in MMSE. A negative change from baseline indicates clinical decline. ITT is defined as all randomised subjects who had received at least one dose of study treatment (Aducanumab or Placebo). Here, 'n' signifies number of subjects analysed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
    Number of subjects analysed
    545
    547
    555
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n=332,334,297)
    -3.5 ± 0.21
    -3.3 ± 0.21
    -3.6 ± 0.21
    Statistical analysis title
    Placebo vs BIIB037 High Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference from Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MMSE as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline MMSE, baseline MMSE by visit interaction, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 High Dose (PC Period)
    Number of subjects included in analysis
    1100
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8106
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.62
         upper limit
    0.49
    Statistical analysis title
    Placebo vs BIIB037 Low Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference from Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MMSE as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline MMSE, baseline MMSE by visit interaction, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 Low Dose (PC Period)
    Number of subjects included in analysis
    1092
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4795
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.35
         upper limit
    0.74

    Secondary: Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 items) (ADAS-Cog 13) Score at Week 78

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    End point title
    Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 items) (ADAS-Cog 13) Score at Week 78
    End point description
    ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The scale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. An increase in score over time indicates increasing cognitive impairment. MMRM analysis was used to analyse change from baseline in ADAS-Cog 13. A positive change from baseline indicates clinical decline. ITT is defined as all randomised subjects who had received at least one dose of study treatment (Aducanumab or Placebo). Here, 'n' signifies number of subjects analysed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
    Number of subjects analysed
    545
    547
    555
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n=331,332,294)
    5.140 ± 0.3783
    4.558 ± 0.3780
    4.552 ± 0.3872
    Statistical analysis title
    Placebo vs BIIB037 High Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo,BIIB037 Low Dose,BIIB037 High Dose),difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in ADAS-Cog 13 as dependent variable and with fixed effects of treatment group,categorical visit,treatment-by-visit interaction,baseline ADAS-Cog 13,baseline ADAS-Cog 13 by visit interaction,baseline MMSE,AD symptomatic medication use at baseline,region,and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 High Dose (PC Period)
    Number of subjects included in analysis
    1100
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2578
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    -0.588
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6067
         upper limit
    0.4309
    Statistical analysis title
    Placebo vs BIIB037 Low Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo,BIIB037 Low Dose,BIIB037 High Dose),difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in ADAS-Cog 13 as dependent variable and with fixed effects of treatment group,categorical visit,treatment-by-visit interaction,baseline ADAS-Cog 13,baseline ADAS-Cog 13 by visit interaction,baseline MMSE,AD symptomatic medication use at baseline,region,and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 Low Dose (PC Period)
    Number of subjects included in analysis
    1092
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2536
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    -0.583
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5835
         upper limit
    0.4181

    Secondary: Change from Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) (ADCS-ADL-MCI) Score at Week 78

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    End point title
    Change from Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) (ADCS-ADL-MCI) Score at Week 78
    End point description
    The ADCS-ADL-MCI consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the patient’s actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53, with lower values over time reflecting functional deterioration. MMRM analysis was used to analyse change from baseline in ADAS-ADL-MCI. A negative change from baseline indicates clinical decline. ITT is defined as all randomised subjects who had received at least one dose of study treatment (Aducanumab or Placebo). Here, 'n' signifies number of subjects analysed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
    Number of subjects analysed
    545
    547
    555
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n=331,330,298)
    -3.8 ± 0.35
    -3.1 ± 0.35
    -3.1 ± 0.35
    Statistical analysis title
    Placebo vs BIIB037 High Dose
    Statistical analysis description
    Adjusted mean for each group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference with Placebo,95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in ADCS-ADL-MCI as dependent variable and with fixed effects of treatment group,categorical visit,treatment-by-visit interaction, baseline ADCS-ADL-MCI, baseline ADCS-ADL-MCI by visit interaction, baseline MMSE AD symptomatic medication use at baseline,region, and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 High Dose (PC Period)
    Number of subjects included in analysis
    1100
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1506
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.25
         upper limit
    1.61
    Statistical analysis title
    Placebo vs BIIB037 Low Dose
    Statistical analysis description
    Adjusted mean for each group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference with Placebo,95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in ADCS-ADL-MCI as dependent variable and with fixed effects of treatment group,categorical visit,treatment-by-visit interaction, baseline ADCS-ADL-MCI, baseline ADCS-ADL-MCI by visit interaction, baseline MMSE AD symptomatic medication use at baseline,region, and laboratory ApoE status.
    Comparison groups
    Placebo (PC Period) v BIIB037 Low Dose (PC Period)
    Number of subjects included in analysis
    1092
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1225
    Method
    MMRM Model
    Parameter type
    Difference from Placebo
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.19
         upper limit
    1.64

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From First Dose to End of Study (up to 4 years)
    Adverse event reporting additional description
    Safety population was all randomised subjects who received at least one dose of study treatment. In PC period, 5 subjects randomised to placebo, inadvertently received 1 or more doses of active treatment during the PC period. For subjects affected, a subject was counted only once within each system organ class/preferred term/study period.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo (PC Period)
    Reporting group description
    Subjects received BIIB037 matching placebo intravenously (IV), once every 4 weeks in PC period for 1.5 years.

    Reporting group title
    BIIB037 Low Dose (PC Period)
    Reporting group description
    Subjects received BIIB037 low dose, IV, once every 4 weeks in PC period for 1.5 years.

    Reporting group title
    BIIB037 High Dose (PC Period)
    Reporting group description
    Subjects received BIIB037 high dose, IV, once every 4 weeks in PC period for 1.5 years.

    Reporting group title
    BIIB037 Late Start: Low Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to placebo received BIIB037 low dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Reporting group title
    BIIB037 Late Start High Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to placebo received BIIB037 high dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period

    Reporting group title
    BIIB037 Early Start: Low Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to low dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Reporting group title
    BIIB037 Early Start: High Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomized to high dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Serious adverse events
    Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE Period) BIIB037 Late Start High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    70 / 540 (12.96%)
    76 / 549 (13.84%)
    79 / 558 (14.16%)
    19 / 150 (12.67%)
    14 / 152 (9.21%)
    35 / 299 (11.71%)
    25 / 251 (9.96%)
         number of deaths (all causes)
    0
    3
    2
    1
    1
    1
    2
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    4 / 558 (0.72%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer stage i
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive papillary breast carcinoma
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    2 / 540 (0.37%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesothelioma
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myeloproliferative neoplasm
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurofibrosarcoma
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cancer stage iii
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polycythaemia vera
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer stage 0
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubular breast carcinoma
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    2 / 150 (1.33%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 540 (0.56%)
    1 / 549 (0.18%)
    2 / 558 (0.36%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised anxiety disorder
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Persistent depressive disorder
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychogenic tremor
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatic dysplasia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Cervical vertebral fracture
         subjects affected / exposed
    2 / 540 (0.37%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Compression fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Exposure to toxic agent
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    6 / 540 (1.11%)
    12 / 549 (2.19%)
    4 / 558 (0.72%)
    4 / 150 (2.67%)
    0 / 152 (0.00%)
    7 / 299 (2.34%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 13
    0 / 4
    0 / 5
    0 / 0
    1 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    2 / 540 (0.37%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 540 (0.19%)
    2 / 549 (0.36%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    2 / 540 (0.37%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heat illness
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    2 / 299 (0.67%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaw fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament injury
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb crushing injury
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    2 / 540 (0.37%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood ketone body increased
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    1 / 150 (0.67%)
    1 / 152 (0.66%)
    2 / 299 (0.67%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    6 / 540 (1.11%)
    4 / 549 (0.73%)
    3 / 558 (0.54%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block right
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    2 / 558 (0.36%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Encephalocele
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal obstruction
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    2 / 299 (0.67%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 540 (0.37%)
    1 / 549 (0.18%)
    3 / 558 (0.54%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood loss anaemia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    2 / 558 (0.36%)
    1 / 150 (0.67%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    4 / 4
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amyloid related imaging abnormality-oedema/effusion
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    7 / 558 (1.25%)
    2 / 150 (1.33%)
    2 / 152 (1.32%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    9 / 9
    2 / 2
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia alzheimer's type
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Dementia with lewy bodies
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dystonia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Focal dyscognitive seizures
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head discomfort
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelitis transverse
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myoclonus
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic intolerance
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peroneal nerve palsy
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    2 / 540 (0.37%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Superficial siderosis of central nervous system
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    2 / 558 (0.36%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 540 (0.37%)
    4 / 549 (0.73%)
    5 / 558 (0.90%)
    1 / 150 (0.67%)
    1 / 152 (0.66%)
    2 / 299 (0.67%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 4
    0 / 5
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 540 (0.19%)
    2 / 549 (0.36%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral artery dissection
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 540 (0.37%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Labyrinthine fistula
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal ulcer
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mallory-weiss syndrome
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic disorder
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc compression
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 540 (0.00%)
    2 / 549 (0.36%)
    2 / 558 (0.36%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    2 / 299 (0.67%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral osteophyte
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 540 (0.37%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    1 / 150 (0.67%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Candida infection
         subjects affected / exposed
    0 / 540 (0.00%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 540 (0.37%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    2 / 558 (0.36%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    2 / 558 (0.36%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    1 / 558 (0.18%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 540 (0.37%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    1 / 540 (0.19%)
    1 / 549 (0.18%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 540 (0.37%)
    1 / 549 (0.18%)
    4 / 558 (0.72%)
    0 / 150 (0.00%)
    1 / 152 (0.66%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 5
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural sepsis
         subjects affected / exposed
    1 / 540 (0.19%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    0 / 299 (0.00%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 540 (0.00%)
    0 / 549 (0.00%)
    0 / 558 (0.00%)
    0 / 150 (0.00%)
    0 / 152 (0.00%)
    1 / 299 (0.33%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection