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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
    2015-000967-15
    Trial protocol
    DE   SE   NL   ES   BE   FR   PL   FI   IT  
    Global end of trial date
    05 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
    221AD302
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02484547
    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
    05 Aug 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Aug 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study is 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 participants with early Alzheimer’s disease.
    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
    15 Sep 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    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
    United States: 652
    Country: Number of subjects enrolled
    Poland: 193
    Country: Number of subjects enrolled
    Germany: 122
    Country: Number of subjects enrolled
    Japan: 121
    Country: Number of subjects enrolled
    Canada: 96
    Country: Number of subjects enrolled
    Italy: 82
    Country: Number of subjects enrolled
    France: 79
    Country: Number of subjects enrolled
    Spain: 78
    Country: Number of subjects enrolled
    Switzerland: 52
    Country: Number of subjects enrolled
    Belgium: 49
    Country: Number of subjects enrolled
    Netherlands: 49
    Country: Number of subjects enrolled
    Sweden: 37
    Country: Number of subjects enrolled
    Finland: 33
    Worldwide total number of subjects
    1643
    EEA total number of subjects
    722
    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)
    324
    From 65 to 84 years
    1303
    85 years and over
    16

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects were enrolled at 181 investigative sites in the United States, Belgium, Canada, Finland, France, Germany, Italy, Japan, Netherlands, Poland, Spain, Sweden, and Switzerland from 15 September 2015 to 13 July 2018.

    Pre-assignment
    Screening details
    A total of 1643 subjects with Alzhiemer’s disease were enrolled and randomised in the study. Of these, 1638 subjects received the study drug in placebo-controlled (PC) period. After completing PC period, 771 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
    Subject, Investigator, Carer, Data analyst, 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
    548
    543
    547
    Completed
    288
    291
    295
    Not completed
    260
    252
    252
         Disease Progression
    2
    -
    1
         Death
    5
    -
    6
         Consent Withdrawn
    15
    32
    26
         Change of Treatment
    -
    -
    1
         Study Visit Burden
    2
    8
    5
         Withdrawal by Parent/Guardian
    4
    1
    1
         Investigator Decision
    2
    2
    5
         Relocation
    1
    1
    1
         Reason not Specified
    216
    194
    183
         Adverse Event
    10
    13
    20
         Lost to follow-up
    3
    1
    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 (548 subjects in placebo arm, 543 subjects in BIIB037 Low Dose arm, 547 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, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    BIIB037 Late Start: Low Dose (LTE Period)
    Arm description
    Following PC period, subjects randomised 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 randomised 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 randomised 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 randomised 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
    131
    132
    251
    257
    Completed
    0
    0
    0
    0
    Not completed
    131
    132
    251
    257
         Death
    -
    -
    3
    -
         Disease Progression
    -
    2
    4
    -
         Consent Withdrawn
    6
    7
    13
    17
         Change of Treatment
    -
    -
    -
    1
         Study Visit Burden
    2
    -
    -
    3
         Withdrawal by Parent/Guardian
    -
    1
    3
    2
         Investigator Decision
    2
    1
    -
    1
         Relocation
    1
    1
    -
    -
         Loss of Capacity
    -
    1
    -
    -
         Reason not Specified
    119
    117
    223
    231
         Adverse Event
    -
    1
    3
    2
         Lost to follow-up
    1
    1
    2
    -
    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: 874 subjects completed the PC period, out of which only 771 subjects entered in LTE period. 103 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
    548 543 547
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    70.8 ± 7.40 70.6 ± 7.45 70.6 ± 7.47 -
    Sex: Female, Male
    Units: subjects
        Female
    290 269 284 843
        Male
    258 274 263 795
    Race
    Units: Subjects
        American Indian or Alaska Native
    1 0 0 1
        Asian
    47 39 42 128
        Black or African American
    1 6 4 11
        White
    431 432 422 1285
        Not Reported due to Confidentiality Regulations
    67 65 75 207
        Other
    1 1 3 5
        Unknown
    0 0 1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    22 22 23 67
        Not Hispanic or Latino
    470 470 461 1401
        Not reported due to confidentiality regulations
    56 51 62 169
        Unknown
    0 0 1 1

    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 randomised 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 randomised 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 randomised 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 randomised 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 Scale - Sum of Boxes (CDR-SB) Score at Week 78

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    End point title
    Change From Baseline in Clinical Dementia Rating Scale - 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
    548
    543
    547
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n =288,290,299)
    1.74 ± 0.115
    1.47 ± 0.116
    1.35 ± 0.115
    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
    1091
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0901
    Method
    mixed model for repeated measures (MMRM)
    Parameter type
    Difference
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.569
         upper limit
    0.041
    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
    Comparison groups
    Placebo (PC Period) v BIIB037 High Dose (PC Period)
    Number of subjects included in analysis
    1095
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012
    Method
    MMRM
    Parameter type
    Difference
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.694
         upper limit
    -0.086

    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
    548
    543
    547
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n =288, 293, 299)
    -3.3 ± 0.22
    -3.3 ± 0.22
    -2.7 ± 0.21
    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
    1091
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7578
    Method
    MMRM
    Parameter type
    Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.65
         upper limit
    0.48
    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
    1095
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0493
    Method
    MMRM
    Parameter type
    Difference
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    1.13

    Secondary: Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 items) (ADAS-Cog 13) 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) 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
    548
    543
    547
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n =287, 289, 293)
    5.162 ± 0.4049
    4.461 ± 0.4074
    3.763 ± 0.4036
    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 ADASCog 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
    1091
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1962
    Method
    MMRM
    Parameter type
    Difference
    Point estimate
    -0.701
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.7649
         upper limit
    0.3627
    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 ADASCog 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
    1095
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0097
    Method
    MMRM
    Parameter type
    Difference
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4596
         upper limit
    -0.3396

    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
    548
    543
    547
    Units: score on a scale
    arithmetic mean (standard error)
        Change at Week 78 (n =283, 286, 295)
    -4.3 ± 0.38
    -3.5 ± 0.38
    -2.5 ± 0.38
    Statistical analysis title
    Placebo vs BIIB037 Low Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo, BIIB037 Low dose and BIIB037 High Dose), difference from Placebo,95% CI and p-value at each time point were based on an MMRM model, with change from baseline in ADCSADL-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
    1091
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1515
    Method
    MMRM
    Parameter type
    Difference
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.27
         upper limit
    1.73
    Statistical analysis title
    Placebo vs BIIB037 High Dose
    Statistical analysis description
    Adjusted mean for each treatment group (Placebo, BIIB037 Low dose and BIIB037 High Dose), difference from Placebo,95% CI and p-value at each time point were based on an MMRM model, with change from baseline in ADCSADL-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
    1095
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0006
    Method
    MMRM
    Parameter type
    Difference
    Point estimate
    1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.75
         upper limit
    2.74

    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,1 subject randomised to placebo, inadvertently received 1 or more doses of active treatment (Low Dose) 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
    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
    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 Late Start: High Dose (LTE Period)
    Reporting group description
    Following PC period, subjects randomised 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 randomised 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 randomised to high 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 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 randomised to placebo received BIIB037 low dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.

    Serious adverse events
    BIIB037 Low Dose (PC Period) Placebo (PC Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE period)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    72 / 544 (13.24%)
    81 / 547 (14.81%)
    9 / 132 (6.82%)
    25 / 251 (9.96%)
    25 / 257 (9.73%)
    73 / 547 (13.35%)
    15 / 131 (11.45%)
         number of deaths (all causes)
    0
    5
    0
    3
    0
    6
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Aortic stenosis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Deep vein thrombosis
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Hypertension
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Hypertensive crisis
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Hypertensive urgency
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Hypotension
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    1 / 132 (0.76%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    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
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Basal cell carcinoma
         subjects affected / exposed
    2 / 544 (0.37%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Bladder papilloma
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Breast cancer
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Cholangiocarcinoma
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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 / 1
    0 / 0
    0 / 0
    0 / 0
    Cholesteatoma
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Diffuse large b-cell lymphoma
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Endometrial cancer
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Gastric cancer
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    Gastrointestinal neoplasm
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Invasive lobular breast carcinoma
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Lung adenocarcinoma stage iv
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Medullary thyroid cancer
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Metastatic neoplasm
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Ovarian cancer
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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 carcinoma metastatic
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Pleural mesothelioma
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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 / 1
    0 / 0
    Prostate cancer
         subjects affected / exposed
    2 / 544 (0.37%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    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
    Prostatic adenoma
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Salivary gland cancer
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Small cell lung cancer
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    T-cell lymphoma
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Thymoma malignant
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Chest pain
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Death
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Discomfort
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Gait disturbance
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    2 / 257 (0.78%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical device site joint pain
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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-cardiac chest pain
         subjects affected / exposed
    1 / 544 (0.18%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 544 (0.00%)
    3 / 547 (0.55%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    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
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Behaviour disorder
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Bipolar disorder
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Confusional state
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    Delirium
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delusion
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Depression
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    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
    Intentional self-injury
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Mania
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Mental status changes
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Neuropsychiatric symptoms
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Psychotic disorder
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Somatic symptom disorder
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Suicidal ideation
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Suicide attempt
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Reproductive system and breast disorders
    Adnexa uteri cyst
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Cervical polyp
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Gynaecomastia
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Ovarian cyst
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Spermatic cord cyst
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Accidental overdose
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Alcohol poisoning
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Animal attack
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Animal scratch
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Ankle fracture
         subjects affected / exposed
    1 / 544 (0.18%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Bone contusion
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Cardiac contusion
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Craniocerebral injury
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Epiphyseal fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Fall
         subjects affected / exposed
    9 / 544 (1.65%)
    12 / 547 (2.19%)
    1 / 132 (0.76%)
    1 / 251 (0.40%)
    6 / 257 (2.33%)
    4 / 547 (0.73%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 12
    0 / 1
    0 / 1
    1 / 6
    0 / 4
    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 / 544 (0.37%)
    3 / 547 (0.55%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    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
    Foot fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Gastrointestinal procedural complication
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Hand fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Head injury
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Hip fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    2 / 257 (0.78%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    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
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Joint dislocation
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    1 / 131 (0.76%)
         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 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Pelvic fracture
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Pubis fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Pulmonary contusion
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Radius fracture
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Rib fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    5 / 547 (0.91%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    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
    Road traffic accident
         subjects affected / exposed
    2 / 544 (0.37%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Skin laceration
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Skull fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Spinal fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Subdural haematoma
         subjects affected / exposed
    3 / 544 (0.55%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Upper limb fracture
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Wrist fracture
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Acute left ventricular failure
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Acute myocardial infarction
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    Angina pectoris
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Angina unstable
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Aortic valve incompetence
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Atrial fibrillation
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    Atrial flutter
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Bradycardia
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Cardiac arrest
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    2 / 257 (0.78%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Myocardial infarction
         subjects affected / exposed
    1 / 544 (0.18%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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 tachycardia
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    1 / 547 (0.18%)
    0 / 131 (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
    Haemothorax
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Laryngeal oedema
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Lung perforation
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Pneumonia aspiration
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Pneumothorax
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Pulmonary embolism
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    Nervous system disorders
    Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits
         subjects affected / exposed
    4 / 544 (0.74%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    4 / 4
    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
    5 / 544 (0.92%)
    1 / 547 (0.18%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    8 / 547 (1.46%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    6 / 6
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    8 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Cerebellar infarction
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         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
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    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
    2 / 544 (0.37%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    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
    Cerebrovascular accident
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Dementia alzheimer's type
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Embolic cerebral infarction
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Embolic stroke
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Encephalopathy
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Focal dyscognitive seizures
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Guillain-barre syndrome
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    Headache
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    1 / 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
    Intracranial venous sinus thrombosis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    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 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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 / 1
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Memory impairment
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Presyncope
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Quadriparesis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Seizure
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sensorimotor disorder
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Superficial siderosis of central nervous system
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    3 / 547 (0.55%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    4 / 4
    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 / 544 (0.37%)
    3 / 547 (0.55%)
    1 / 132 (0.76%)
    2 / 251 (0.80%)
    2 / 257 (0.78%)
    4 / 547 (0.73%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 2
    0 / 4
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombotic stroke
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    Toxic encephalopathy
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Transient ischaemic attack
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    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
    Eye disorders
    Age-related macular degeneration
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Cataract nuclear
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Retinal detachment
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Vitreous floaters
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Ear and labyrinth disorders
    Deafness bilateral
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Meniere's disease
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    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
    Vertigo
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Acquired oesophageal web
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Barrett's oesophagus
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Colitis
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Colitis ischaemic
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Constipation
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Diarrhoea
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Diverticular perforation
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Duodenal ulcer perforation
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Dysphagia
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Femoral hernia strangulated
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    2 / 544 (0.37%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    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
    Haemorrhoids
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Ileus
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Inguinal hernia
         subjects affected / exposed
    2 / 544 (0.37%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    3 / 547 (0.55%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         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 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Large intestine polyp
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    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
    Nausea
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Obstructive pancreatitis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
         subjects affected / exposed
    1 / 544 (0.18%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Pancreatitis acute
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Pneumoperitoneum
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Rectal prolapse
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Calculus bladder
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Nephrolithiasis
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    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
    Prerenal failure
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Renal failure
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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 / 1
    0 / 0
    Urethral disorder
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Urethral stenosis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Urinary retention
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Cholecystitis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Cholecystitis acute
         subjects affected / exposed
    0 / 544 (0.00%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Cholelithiasis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Hepatitis acute
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Jaundice
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Back pain
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Bursitis
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Muscular weakness
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Musculoskeletal pain
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    3 / 544 (0.55%)
    2 / 547 (0.37%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    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
    Osteonecrosis
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
    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 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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 osteoarthritis
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Vertebral foraminal stenosis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Hyperglycaemia
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Hyponatraemia
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 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
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Bacterial infection
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Bronchitis
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis klebsiella
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Erysipelas
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Gastroenteritis viral
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    1 / 547 (0.18%)
    0 / 131 (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
    Human anaplasmosis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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
    Lymphangitis
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Otitis media
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Pneumonia
         subjects affected / exposed
    2 / 544 (0.37%)
    2 / 547 (0.37%)
    1 / 132 (0.76%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
    0 / 1
    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
    Pneumonia bacterial
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    1 / 131 (0.76%)
         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
    Pneumonia influenzal
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    0 / 547 (0.00%)
    0 / 131 (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
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 544 (0.18%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Pulmonary sepsis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (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 / 1
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 544 (0.00%)
    0 / 547 (0.00%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    1 / 257 (0.39%)
    2 / 547 (0.37%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    Urinary tract infection
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    1 / 251 (0.40%)
    0 / 257 (0.00%)
    1 / 547 (0.18%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    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
    Urosepsis
         subjects affected / exposed
    0 / 544 (0.00%)
    1 / 547 (0.18%)
    0 / 132 (0.00%)
    0 / 251 (0.00%)
    0 / 257 (0.00%)
    0 / 547 (0.00%)
    0 / 131 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    BIIB037 Low Dose (PC Period) Placebo (PC Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE period)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    385 / 544 (70.77%)
    353 / 547 (64.53%)
    56 / 132 (42.42%)
    87 / 251 (34.66%)
    107 / 257 (41.63%)
    428 / 547 (78.24%)
    55 / 131 (41.98%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    59 / 544 (10.85%)
    62 / 547 (11.33%)
    7 / 132 (5.30%)
    15 / 251 (5.98%)
    32 / 257 (12.45%)
    73 / 547 (13.35%)
    13 / 131 (9.92%)
         occurrences all number
    82
    86
    8
    16
    49
    109
    18
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    24 / 544 (4.41%)
    28 / 547 (5.12%)
    4 / 132 (3.03%)
    7 / 251 (2.79%)
    14 / 257 (5.45%)
    33 / 547 (6.03%)
    4 / 131 (3.05%)
         occurrences all number
    28
    31
    4
    7
    15
    36
    4
    Nervous system disorders