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    Clinical Trial Results:
    Efficacy and safety of 3 doses of S 47445 versus placebo in patients with Alzheimer's disease at mild to moderate stages with depressive symptoms. A 24-week international, multi-centre, randomized, double-blind, placebo-controlled phase II study in monotherapy followed by an optional 28-week extension period in co-administration with donepezil.

    Summary
    EudraCT number
    		 2014-001519-38
    Trial protocol
    		 DE   CZ   HU   BG   SK  
    Global end of trial date
    20 Sep 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Jul 2018
    First version publication date
    18 Jul 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CL2-47445-011
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02626572
    WHO universal trial number (UTN)
    		 U1111-1156-1378
    Sponsors
    Sponsor organisation name
    Institut de Recherches Internationales Servier
    Sponsor organisation address
    50 rue Carnot, Suresnes, France, 92284
    Public contact
    Clinical Studies Department, Institut de Recherches Internationales Servier, 33 0155724366, clinicaltrials@servier.com
    Scientific contact
    Clinical Studies Department, Institut de Recherches Internationales Servier, 33 0155724366, clinicaltrials@servier.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
    20 Sep 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Sep 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Sep 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Assessment of efficacy of 3 doses of S 47445 versus placebo on cognitive performance measured with the 11-item ADAS-Cog after 24 weeks of treatment.
    Protection of trial subjects
    This study was conducted in accordance with Good Clinical Practice standards, ethical principles stated in the Declaration of Helsinki and applicable regulatory requirements. After the subject has ended his/her participation in the trial, the investigator provided appropriate medication and/or arranged access to appropriate care for the patient.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Feb 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 37
    Country: Number of subjects enrolled
    Slovakia: 11
    Country: Number of subjects enrolled
    Bulgaria: 56
    Country: Number of subjects enrolled
    Czech Republic: 66
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Hungary: 63
    Country: Number of subjects enrolled
    Brazil: 48
    Country: Number of subjects enrolled
    Chile: 83
    Country: Number of subjects enrolled
    Japan: 4
    Country: Number of subjects enrolled
    Mexico: 28
    Country: Number of subjects enrolled
    Russian Federation: 73
    Country: Number of subjects enrolled
    South Africa: 19
    Worldwide total number of subjects
    520
    EEA total number of subjects
    265
    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)
    100
    From 65 to 84 years
    415
    85 years and over
    5

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Male or female patients aged from 55 to 85 years suffering from mild to moderate Alzheimer’s disease (AD) with depressive symptoms.

    Period 1
    Period 1 title
    24-week treatment period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 S 47445 5 mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    S 47445 5 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet of S47445 5 mg was administered once a day during breakfast with a glass of water.

    Arm title
    		 S 47445 15 mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    S 47445 15 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet of S47445 15 mg was administered once a day during breakfast with a glass of water.

    Arm title
    		 S 47445 50 mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    S 47445 50 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet of S47445 50 mg was administered once a day during breakfast with a glass of water.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet of placebo was administered once a day during breakfast with a glass of water.

    Number of subjects in period 1
    		S 47445 5 mg S 47445 15 mg S 47445 50 mg Placebo
    Started
    129
    130
    132
    129
    Completed
    120
    116
    116
    119
    Not completed
    9
    14
    16
    10
         Adverse event, serious fatal
    -
    1
    2
    3
         Adverse event, non-fatal
    1
    5
    5
    3
         Lost to follow-up
    1
    -
    -
    -
         Non-medical reason
    6
    7
    5
    4
         Lack of efficacy
    1
    1
    3
    -
         Protocol deviation
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    S 47445 5 mg
    Reporting group description
    		 -

    Reporting group title
    S 47445 15 mg
    Reporting group description
    		 -

    Reporting group title
    S 47445 50 mg
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group values
    		 S 47445 5 mg S 47445 15 mg S 47445 50 mg Placebo Total
    Number of subjects
    		 129 130 132 129 520
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.2 ± 7.3 71.7 ± 7.7 71.8 ± 6.6 71.4 ± 7.7 -
    Gender categorical
    Units: Subjects
        Female
    		 82 96 95 90 363
        Male
    		 47 34 37 39 157

    End points

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    End points reporting groups
    Reporting group title
    S 47445 5 mg
    Reporting group description
    		 -

    Reporting group title
    S 47445 15 mg
    Reporting group description
    		 -

    Reporting group title
    S 47445 50 mg
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Primary: 11-item ADAS-Cog total score

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    End point title
    		 11-item ADAS-Cog total score
    End point description
    End point type
    Primary
    End point timeframe
    The main analytical approach was the change from baseline to week 24.
    End point values
    		 S 47445 5 mg S 47445 15 mg S 47445 50 mg Placebo
    Number of subjects analysed
    120
    118
    121
    121
    Units: No unit
        arithmetic mean (standard deviation)
    -0.20 ± 4.91
    -0.74 ± 5.43
    -0.05 ± 5.82
    0.35 ± 5.53
    Statistical analysis title
    		 Primary analysis
    Statistical analysis description
    All the longitudinal observations at each post-baseline visit during the 24-week treatment period were considered.
    Comparison groups
    S 47445 5 mg v Placebo
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.83
         upper limit
    		 0.89
    Variability estimate
    Standard deviation
    Dispersion value
    0.69
    Statistical analysis title
    		 Primary analysis
    Statistical analysis description
    All the longitudinal observations at each post-baseline visit during the 24-week treatment period were considered.
    Comparison groups
    S 47445 15 mg v Placebo
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.26
         upper limit
    		 0.46
    Variability estimate
    Standard deviation
    Dispersion value
    0.69
    Statistical analysis title
    		 Primary analysis
    Statistical analysis description
    All the longitudinal observations at each post-baseline visit during the 24-week treatment period were considered.
    Comparison groups
    S 47445 50 mg v Placebo
    Number of subjects included in analysis
    242
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 1.01
    Variability estimate
    Standard deviation
    Dispersion value
    0.69

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events that occurred or worsened or became serious during the treatment periods defined as below.
    Adverse event reporting additional description
    Between the first and the last study drug intake date (both included) during the 24-week mandatory treatment period, Between the first and the last study drug intake + 15 days (both included) during the 28-week optional extension treatment period and during the 52-week treatment period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20
    Reporting groups
    Reporting group title
    S 47445 5 mg - W0-W24
    Reporting group description
    		 -

    Reporting group title
    S 47445 15 mg - W0-W24
    Reporting group description
    		 -

    Reporting group title
    S 47445 50 mg - W0-W24
    Reporting group description
    		 -

    Reporting group title
    Placebo - W0-W24
    Reporting group description
    		 -

    Reporting group title
    S 47445 5 mg - W24-W52
    Reporting group description
    		 -

    Reporting group title
    S 47445 15 mg - W24-W52
    Reporting group description
    		 -

    Reporting group title
    S 47445 50 mg - W24-W52
    Reporting group description
    		 -

    Reporting group title
    Placebo - W24-W52
    Reporting group description
    		 -

    Reporting group title
    S 47445 5 mg - W0-W52
    Reporting group description
    		 -

    Reporting group title
    S 47445 15 mg - W0-W52
    Reporting group description
    		 -

    Reporting group title
    S 47445 50 mg - W0-W52
    Reporting group description
    		 -

    Reporting group title
    Placebo - W0-W52
    Reporting group description
    		 -

    Serious adverse events
    		 S 47445 5 mg - W0-W24 S 47445 15 mg - W0-W24 S 47445 50 mg - W0-W24 Placebo - W0-W24 S 47445 5 mg - W24-W52 S 47445 15 mg - W24-W52 S 47445 50 mg - W24-W52 Placebo - W24-W52 S 47445 5 mg - W0-W52 S 47445 15 mg - W0-W52 S 47445 50 mg - W0-W52 Placebo - W0-W52
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 129 (3.10%)
    11 / 130 (8.46%)
    5 / 132 (3.79%)
    6 / 129 (4.65%)
    8 / 119 (6.72%)
    16 / 115 (13.91%)
    10 / 115 (8.70%)
    10 / 119 (8.40%)
    11 / 129 (8.53%)
    27 / 130 (20.77%)
    16 / 132 (12.12%)
    17 / 129 (13.18%)
         number of deaths (all causes)
    0
    0
    1
    1
    0
    1
    1
    2
    0
    1
    2
    3
         number of deaths resulting from adverse events
    1
    1
    1
    1
    2
    1
    2
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal cancer stage IV
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cystocele
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchitis chronic
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delusion
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination, visual
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Middle insomnia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram abnormal
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Brain contusion
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    6 / 115 (5.22%)
    1 / 115 (0.87%)
    2 / 119 (1.68%)
    3 / 129 (2.33%)
    7 / 130 (5.38%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 1
    0 / 2
    0 / 3
    0 / 7
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    2 / 115 (1.74%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    2 / 115 (1.74%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve sclerosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    2 / 119 (1.68%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    3 / 129 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure chronic
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve sclerosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amimia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradykinesia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cogwheel rigidity
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Dementia with Lewy bodies
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Loss of consciousness
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Sciatica
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural hygroma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
    alternative dictionary used: MedDRA 19
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Haemorrhagic anaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Macular degeneration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mastoiditis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1.5%
    Non-serious adverse events
    		 S 47445 5 mg - W0-W24 S 47445 15 mg - W0-W24 S 47445 50 mg - W0-W24 Placebo - W0-W24 S 47445 5 mg - W24-W52 S 47445 15 mg - W24-W52 S 47445 50 mg - W24-W52 Placebo - W24-W52 S 47445 5 mg - W0-W52 S 47445 15 mg - W0-W52 S 47445 50 mg - W0-W52 Placebo - W0-W52
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    59 / 129 (45.74%)
    49 / 130 (37.69%)
    66 / 132 (50.00%)
    60 / 129 (46.51%)
    50 / 119 (42.02%)
    42 / 115 (36.52%)
    41 / 115 (35.65%)
    41 / 119 (34.45%)
    78 / 129 (60.47%)
    70 / 130 (53.85%)
    79 / 132 (59.85%)
    76 / 129 (58.91%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    3 / 129 (2.33%)
    2 / 119 (1.68%)
    2 / 115 (1.74%)
    2 / 115 (1.74%)
    3 / 119 (2.52%)
    5 / 129 (3.88%)
    4 / 130 (3.08%)
    3 / 132 (2.27%)
    7 / 129 (5.43%)
         occurrences all number
    2
    2
    1
    3
    2
    2
    2
    3
    5
    4
    3
    7
    Orthostatic hypotension
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 130 (2.31%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    4 / 130 (3.08%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    1
    1
    0
    1
    4
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    3 / 119 (2.52%)
    2 / 115 (1.74%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    3 / 129 (2.33%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    0
    1
    3
    2
    1
    0
    3
    2
    1
    1
    Fatigue
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    3 / 129 (2.33%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    1
    1
    0
    1
    1
    3
    Oedema peripheral
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    1
    0
    0
    2
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    0
    2
    1
    0
    0
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    2 / 115 (1.74%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    2
    0
    0
    0
    2
    1
    Anxiety
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    1
    0
    0
    2
    1
    1
    Confusional state
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences all number
    1
    0
    0
    3
    0
    0
    0
    0
    1
    0
    0
    3
    Delusion
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    1
    2
    0
    0
    2
    2
    Depression
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    2 / 132 (1.52%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    1
    2
    0
    1
    1
    0
    0
    1
    2
    2
    Initial insomnia
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    3 / 129 (2.33%)
         occurrences all number
    2
    0
    0
    2
    0
    0
    0
    1
    2
    0
    0
    3
    Insomnia
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    2 / 115 (1.74%)
    1 / 119 (0.84%)
    2 / 129 (1.55%)
    2 / 130 (1.54%)
    3 / 132 (2.27%)
    2 / 129 (1.55%)
         occurrences all number
    1
    2
    1
    1
    1
    0
    2
    1
    2
    2
    3
    2
    Irritability
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
         occurrences all number
    1
    1
    0
    2
    1
    1
    1
    0
    2
    2
    1
    2
    Mood altered
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    0
    Nightmare
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    1
    1
    2
    0
    1
    2
    Suicidal ideation
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    0
    0
    0
    2
    1
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    2
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    2
    0
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    6 / 132 (4.55%)
    4 / 129 (3.10%)
    5 / 119 (4.20%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    2 / 119 (1.68%)
    7 / 129 (5.43%)
    2 / 130 (1.54%)
    6 / 132 (4.55%)
    6 / 129 (4.65%)
         occurrences all number
    2
    1
    7
    4
    5
    1
    0
    2
    7
    2
    7
    6
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
         occurrences all number
    0
    1
    1
    2
    0
    0
    0
    0
    0
    1
    1
    2
    Blood pressure increased
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    3 / 130 (2.31%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
         occurrences all number
    1
    3
    2
    1
    0
    1
    0
    0
    1
    4
    3
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    2 / 119 (1.68%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    4 / 129 (3.10%)
    3 / 130 (2.31%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    2
    2
    1
    1
    2
    1
    0
    0
    4
    3
    1
    1
    Weight decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 130 (2.31%)
    2 / 132 (1.52%)
    2 / 129 (1.55%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    4 / 130 (3.08%)
    2 / 132 (1.52%)
    3 / 129 (2.33%)
         occurrences all number
    0
    3
    2
    2
    1
    1
    1
    1
    1
    4
    2
    3
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 130 (0.77%)
    3 / 132 (2.27%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    2 / 115 (1.74%)
    2 / 115 (1.74%)
    2 / 119 (1.68%)
    3 / 129 (2.33%)
    2 / 130 (1.54%)
    5 / 132 (3.79%)
    3 / 129 (2.33%)
         occurrences all number
    3
    4
    3
    1
    0
    2
    3
    2
    3
    6
    6
    3
    Concussion
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    2 / 115 (1.74%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    0
    0
    1
    2
    0
    0
    Contusion
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    3 / 130 (2.31%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    1
    1
    0
    0
    3
    2
    0
    Fall
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 130 (2.31%)
    3 / 132 (2.27%)
    2 / 129 (1.55%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    2 / 115 (1.74%)
    2 / 119 (1.68%)
    3 / 129 (2.33%)
    4 / 130 (3.08%)
    5 / 132 (3.79%)
    4 / 129 (3.10%)
         occurrences all number
    2
    3
    3
    2
    1
    1
    2
    2
    3
    4
    5
    4
    Ligament sprain
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    1
    2
    Procedural pain
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Traumatic haematoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    2 / 132 (1.52%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    1
    1
    0
    1
    2
    2
    Cardiac disorders
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    0
    0
    2
    1
    0
    0
    Bundle branch block left
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    3 / 129 (2.33%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    3 / 129 (2.33%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    3
    Bundle branch block right
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    0
    0
    1
    0
    2
    Sinus bradycardia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    3 / 132 (2.27%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    1
    1
    0
    0
    3
    2
    Sinus tachycardia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    2
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    1
    1
    0
    0
    2
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    2
    0
    0
    0
    Dementia Alzheimer's type
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    0
    0
    2
    0
    2
    0
    Dizziness
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    2 / 115 (1.74%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    3 / 130 (2.31%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences all number
    1
    2
    2
    0
    0
    1
    2
    0
    1
    3
    4
    0
    Dizziness exertional
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    3 / 130 (2.31%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    1
    0
    0
    1
    3
    0
    0
    Dizziness postural
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
    4 / 119 (3.36%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    5 / 129 (3.88%)
    2 / 130 (1.54%)
    2 / 132 (1.52%)
    3 / 129 (2.33%)
         occurrences all number
    2
    1
    1
    2
    6
    1
    1
    1
    8
    2
    2
    3
    Headache
         subjects affected / exposed
    3 / 129 (2.33%)
    4 / 130 (3.08%)
    4 / 132 (3.03%)
    5 / 129 (3.88%)
    5 / 119 (4.20%)
    3 / 115 (2.61%)
    1 / 115 (0.87%)
    3 / 119 (2.52%)
    7 / 129 (5.43%)
    8 / 130 (6.15%)
    5 / 132 (3.79%)
    7 / 129 (5.43%)
         occurrences all number
    4
    4
    4
    5
    5
    3
    1
    4
    9
    8
    5
    9
    Tension headache
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 130 (2.31%)
    0 / 132 (0.00%)
    3 / 129 (2.33%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    3 / 130 (2.31%)
    0 / 132 (0.00%)
    4 / 129 (3.10%)
         occurrences all number
    0
    3
    0
    3
    0
    0
    0
    1
    0
    3
    0
    4
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    2 / 115 (1.74%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    2
    0
    0
    1
    2
    1
    0
    Leukopenia
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    3 / 132 (2.27%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    3 / 132 (2.27%)
    0 / 129 (0.00%)
         occurrences all number
    1
    1
    3
    0
    0
    1
    1
    0
    1
    2
    4
    0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    0
    Vertigo positional
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    0
    0
    2
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    2
    0
    0
    0
    1
    0
    1
    1
    3
    0
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    4 / 132 (3.03%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    3 / 132 (2.27%)
    0 / 129 (0.00%)
         occurrences all number
    3
    1
    4
    0
    0
    0
    0
    0
    3
    1
    3
    0
    Constipation
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    4 / 129 (3.10%)
    5 / 119 (4.20%)
    6 / 115 (5.22%)
    1 / 115 (0.87%)
    2 / 119 (1.68%)
    6 / 129 (4.65%)
    8 / 130 (6.15%)
    2 / 132 (1.52%)
    6 / 129 (4.65%)
         occurrences all number
    1
    2
    1
    4
    5
    6
    1
    2
    6
    8
    2
    6
    Diverticulum intestinal
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    2 / 119 (1.68%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    2
    Dry mouth
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    3 / 132 (2.27%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    1
    1
    1
    0
    3
    1
    Gastritis
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    2 / 132 (1.52%)
    2 / 129 (1.55%)
         occurrences all number
    1
    1
    0
    1
    0
    0
    1
    1
    1
    1
    2
    2
    Nausea
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    5 / 119 (4.20%)
    6 / 115 (5.22%)
    3 / 115 (2.61%)
    5 / 119 (4.20%)
    8 / 129 (6.20%)
    7 / 130 (5.38%)
    4 / 132 (3.03%)
    6 / 129 (4.65%)
         occurrences all number
    3
    2
    1
    1
    9
    6
    3
    5
    12
    8
    4
    6
    Vomiting
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    2 / 119 (1.68%)
    2 / 115 (1.74%)
    3 / 115 (2.61%)
    2 / 119 (1.68%)
    3 / 129 (2.33%)
    2 / 130 (1.54%)
    3 / 132 (2.27%)
    2 / 129 (1.55%)
         occurrences all number
    1
    0
    0
    0
    2
    2
    3
    2
    3
    2
    3
    2
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    1
    0
    0
    0
    2
    1
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    2
    0
    1
    1
    1
    1
    0
    0
    3
    1
    1
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    4 / 115 (3.48%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    4 / 130 (3.08%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    1
    0
    1
    4
    0
    1
    1
    4
    1
    1
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    2
    1
    0
    2
    2
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    3 / 132 (2.27%)
    2 / 129 (1.55%)
         occurrences all number
    0
    2
    2
    1
    0
    0
    1
    1
    0
    2
    3
    2
    Bronchitis bacterial
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    2
    Bronchitis viral
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Cystitis
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    0
    0
    0
    2
    1
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    2
    Influenza
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    4 / 119 (3.36%)
    2 / 129 (1.55%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    6 / 129 (4.65%)
         occurrences all number
    1
    0
    1
    2
    1
    1
    0
    4
    2
    1
    1
    6
    Nasopharyngitis
         subjects affected / exposed
    4 / 129 (3.10%)
    3 / 130 (2.31%)
    7 / 132 (5.30%)
    6 / 129 (4.65%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    4
    3
    9
    7
    0
    0
    0
    0
    1
    0
    0
    0
    Periodontitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    2 / 115 (1.74%)
    1 / 115 (0.87%)
    2 / 119 (1.68%)
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    1
    2
    1
    2
    1
    2
    Rhinitis
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
         occurrences all number
    3
    0
    1
    1
    0
    0
    0
    0
    3
    0
    1
    1
    Urinary tract infection
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    6 / 129 (4.65%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    4 / 129 (3.10%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    7 / 129 (5.43%)
         occurrences all number
    4
    0
    1
    8
    3
    0
    0
    2
    7
    0
    1
    10
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    6 / 119 (5.04%)
    2 / 115 (1.74%)
    3 / 115 (2.61%)
    0 / 119 (0.00%)
    8 / 129 (6.20%)
    5 / 130 (3.85%)
    9 / 132 (6.82%)
    6 / 129 (4.65%)
         occurrences all number
    0
    0
    0
    0
    6
    2
    3
    0
    9
    5
    13
    7
    Metabolism and nutrition disorders
    Acquired mixed hyperlipidaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    0
    1
    0
    1
    1
    2
    Decreased appetite
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    4 / 115 (3.48%)
    2 / 115 (1.74%)
    1 / 119 (0.84%)
    2 / 129 (1.55%)
    6 / 130 (4.62%)
    3 / 132 (2.27%)
    1 / 129 (0.78%)
         occurrences all number
    1
    2
    1
    0
    1
    4
    2
    1
    2
    6
    3
    1
    Dyslipidaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    2
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 130 (0.77%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    2 / 119 (1.68%)
    3 / 115 (2.61%)
    2 / 115 (1.74%)
    0 / 119 (0.00%)
    4 / 129 (3.10%)
    4 / 130 (3.08%)
    2 / 132 (1.52%)
    1 / 129 (0.78%)
         occurrences all number
    1
    1
    0
    1
    2
    3
    2
    0
    4
    4
    2
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 130 (2.31%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    1 / 115 (0.87%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    4 / 130 (3.08%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences all number
    1
    3
    2
    0
    1
    1
    0
    0
    2
    4
    2
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 130 (0.00%)
    1 / 132 (0.76%)
    2 / 129 (1.55%)
    2 / 119 (1.68%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    6 / 129 (4.65%)
    0 / 130 (0.00%)
    2 / 132 (1.52%)
    3 / 129 (2.33%)
         occurrences all number
    3
    0
    1
    2
    3
    0
    1
    1
    7
    0
    2
    3
    Hyperuricaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    2 / 115 (1.74%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    0
    0
    2
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
    1 / 119 (0.84%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    2 / 129 (1.55%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    0 / 129 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    0
    0
    3
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    0 / 115 (0.00%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    0
    0
    0
    2
    1
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 130 (0.00%)
    0 / 132 (0.00%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    2 / 115 (1.74%)
    3 / 115 (2.61%)
    1 / 119 (0.84%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    3 / 132 (2.27%)
    1 / 129 (0.78%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    3
    1
    0
    2
    3
    2
    Malnutrition
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    0 / 129 (0.00%)
    0 / 119 (0.00%)
    1 / 115 (0.87%)
    1 / 115 (0.87%)
    0 / 119 (0.00%)
    0 / 129 (0.00%)
    2 / 130 (1.54%)
    2 / 132 (1.52%)
    0 / 129 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    1
    0
    0
    2
    2
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    4 / 129 (3.10%)
    1 / 130 (0.77%)
    1 / 132 (0.76%)
    1 / 129 (0.78%)
    0 / 119 (0.00%)
    0 / 115 (0.00%)
    1 / 115 (0.87%)
    1 / 119 (0.84%)
    4 / 129 (3.10%)
    1 / 130 (0.77%)
    2 / 132 (1.52%)
    2 / 129 (1.55%)
         occurrences all number
    4
    1
    1
    1
    0
    0
    1
    1
    4
    1
    2
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Feb 2015
    Update of the inclusion criterion related to estimated Glomerular Filtration Rate (GFR) calculation.
    09 Dec 2015
    During the optional extension period, the decrease of donepezil dose from 10 mg to 5 mg was permitted if necessary between weeks 28 and 38. Once dose of donepezil decreased to 5 mg, the investigator did not have the possibility to return to 10 mg.
    29 Feb 2016
    Recruitment in Japan was closed further to recruitment difficulties. New countries were added to the list of participating countries in order to reach the planned target of total patients.
    10 Nov 2016
    Update of the list of concomitant treatments with addition of BCRP substrates.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    26 Jun 2017
    The main analysis was done in June 2017 with full efficacy and safety data of the mandatory 24-week treatment period. Based on these results, the Sponsor decided to discontinue the study and the development of S47445 in Alzheimer’s Disease.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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