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    Clinical Trial Results:
    A Clinical Outcomes Study to compare the effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg with placebo on Survival in Subjects with moderate Chronic Obstructive Pulmonary Disease (COPD) and a history of or at increased risk for cardiovascular disease.

    Summary
    EudraCT number
    		 2010-021638-72
    Trial protocol
    		 CZ   SK   LV   AT   DE   GB   DK   PL   GR   BG   ES   IT   NL   BE  
    Global end of trial date
    15 Jul 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Mar 2016
    First version publication date
    31 Mar 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    HZC113782
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01313676
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 N/A: N/A
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    Clincial Trails Helpdesk, GlaxoSmithKline Research & Development Ltd, +44 0208990 44 66, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clincial Trails Helpdesk, GlaxoSmithKline Research & Development Ltd, +44 0208990 44 66, GSKClinicalSupportHD@gsk.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
    07 Sep 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to prospectively evaluate the effect of Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25mcg QD compared with placebo on survival in subjects with moderate COPD (≥50 and ≤70 % predicted FEV1) and a history of, or at increased risk for developing, cardiovascular disease.
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Jan 2011
    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
    Argentina: 711
    Country: Number of subjects enrolled
    Australia: 77
    Country: Number of subjects enrolled
    Austria: 149
    Country: Number of subjects enrolled
    Hungary: 352
    Country: Number of subjects enrolled
    India: 476
    Country: Number of subjects enrolled
    Indonesia: 203
    Country: Number of subjects enrolled
    Israel: 85
    Country: Number of subjects enrolled
    Belarus: 26
    Country: Number of subjects enrolled
    Belgium: 12
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 453
    Country: Number of subjects enrolled
    Bulgaria: 717
    Country: Number of subjects enrolled
    Canada: 125
    Country: Number of subjects enrolled
    Chile: 93
    Country: Number of subjects enrolled
    China: 742
    Country: Number of subjects enrolled
    Colombia: 175
    Country: Number of subjects enrolled
    Croatia: 350
    Country: Number of subjects enrolled
    Czech Republic: 602
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    Georgia: 620
    Country: Number of subjects enrolled
    Germany: 840
    Country: Number of subjects enrolled
    Greece: 57
    Country: Number of subjects enrolled
    Japan: 239
    Country: Number of subjects enrolled
    Korea, Republic of: 275
    Country: Number of subjects enrolled
    Latvia: 449
    Country: Number of subjects enrolled
    Macedonia, the former Yugoslav Republic of: 766
    Country: Number of subjects enrolled
    Malaysia: 42
    Country: Number of subjects enrolled
    Mexico: 156
    Country: Number of subjects enrolled
    Netherlands: 16
    Country: Number of subjects enrolled
    Philippines: 1262
    Country: Number of subjects enrolled
    Poland: 1850
    Country: Number of subjects enrolled
    Romania: 712
    Country: Number of subjects enrolled
    Russian Federation: 1578
    Country: Number of subjects enrolled
    Serbia: 246
    Country: Number of subjects enrolled
    Slovakia: 151
    Country: Number of subjects enrolled
    South Africa: 647
    Country: Number of subjects enrolled
    Spain: 195
    Country: Number of subjects enrolled
    Taiwan: 79
    Country: Number of subjects enrolled
    Thailand: 162
    Country: Number of subjects enrolled
    Turkey: 43
    Country: Number of subjects enrolled
    Ukraine: 1482
    Country: Number of subjects enrolled
    United Kingdom: 245
    Country: Number of subjects enrolled
    United States: 6132
    Country: Number of subjects enrolled
    Vietnam: 231
    Worldwide total number of subjects
    23835
    EEA total number of subjects
    6709
    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)
    10578
    From 65 to 84 years
    13257
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 1373 sites. The study employed an event-driven design and was to conclude when approximately 1000 reports of a primary outcome event of death were received. The study consisted of a 4-10 day run-in period, variable treatment period until the required number of events was achieved, and 1 week follow-up period.

    Pre-assignment
    Screening details
    		 A total of 23,835 participants were screened, of whom 16,590 were randomized. Of the 16,590 participants randomized, 16,568 participants received a single dose of investigational product (IP) and were assigned to a treatment and included in the Safety Population.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo once daily (OD) in the morning from the dry powder inhaler (DPI) until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
    Arm type
    		 Placebo Comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    The formulation is available in two strips. First strip contains lactose and second strip contains blend of lactose and magnesium stearate. The formulation was an inhaler (ELLIPTA) which contained 30 doses. It was administered once daily via dry powder inhaler in morning.

    Arm title
    		 Fluticasone furoate 100 µg
    Arm description
    		 Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fluticasone furoate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Formulation is available in two strips and contains 100µg fluticasone furoate per blister. First strip contains fluticasone furoate blended with lactose and second strip contains blend of lactose and magnesium stearate. The formulation was an inhaler (ELLIPTA) which contained 30 doses. It was administered as 100µg dose once daily via dry powder inhaler in morning.

    Arm title
    		 Vilanterol 25 µg
    Arm description
    		 Participants received Vilanterol (VI) 25 µg inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vilanterol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Formulation is available in two strips and contains 25µg vilanterol per blister. First strip contains vilanterol blended with lactose and magnesium stearate and second strip contains lactose. The formulation was an inhaler (ELLIPTA) which contained 30 doses. It was administered as 25µg dose once daily via dry powder inhaler in morning.

    Arm title
    		 Fluticasone furoate/vilanterol 100/25 µg
    Arm description
    		 Participants received FF/VI 100/25 µg inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fluticasone furoate/vilanterol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Formulation is available in two strips and contains 100µg fluticasone furoate/25µg vilanterol per blister. First strip contains fluticasone furoate blended with lactose and second strip contains vilanterol blended with lactose and magnesium stearate. The formulation was an inhaler (ELLIPTA) which contained 30 doses. It was administered as 100µg/25µg dose once daily via dry powder inhaler in morning.

    Number of subjects in period 1 [1]
    		Placebo Fluticasone furoate 100 µg Vilanterol 25 µg Fluticasone furoate/vilanterol 100/25 µg
    Started
    4131
    4157
    4140
    4140
    Completed
    2881
    3044
    3052
    3146
    Not completed
    1250
    1113
    1088
    994
         Physician decision
    53
    64
    62
    48
         Adverse Event
    395
    365
    372
    333
         Decision by Participant or Proxy
    643
    527
    515
    492
         Met Protocol-Defined Stopping Critera
    3
    4
    2
    11
         Study Closed/terminated
    7
    6
    9
    9
         Sponsor Terminated Study Treatment
    1
    1
    -
    1
         Investigator Site Closed
    12
    11
    15
    10
         Lost to follow-up
    -
    -
    1
    -
         Missing
    1
    1
    1
    -
         Lack of efficacy
    98
    90
    65
    46
         Protocol deviation
    37
    44
    46
    44
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 23,835 participants were screened, of whom 16,590 were randomized. Of the 16,590 participants randomized, 16,568 participants received a single dose of investigational product (IP) and were assigned to a treatment and included in the Safety Population.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo once daily (OD) in the morning from the dry powder inhaler (DPI) until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Reporting group title
    Fluticasone furoate 100 µg
    Reporting group description
    		 Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Reporting group title
    Vilanterol 25 µg
    Reporting group description
    		 Participants received Vilanterol (VI) 25 µg inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Reporting group title
    Fluticasone furoate/vilanterol 100/25 µg
    Reporting group description
    		 Participants received FF/VI 100/25 µg inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Reporting group values
    		 Placebo Fluticasone furoate 100 µg Vilanterol 25 µg Fluticasone furoate/vilanterol 100/25 µg Total
    Number of subjects
    		 4131 4157 4140 4140 16568
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        geometric mean (standard deviation)
    		 65.2 ( 7.9 ) 65 ( 8.02 ) 65.2 ( 7.68 ) 65.3 ( 7.97 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1050 1098 1071 1019 4238
        Male
    		 3081 3059 3069 3121 12330
    Race, Customized
    Units: Subjects
        African American /African Heritage
    		 61 62 68 69 260
        American Indian or Alaskan Native
    		 9 5 4 9 27
        Asian - Central /South Asian Heritage
    		 64 55 62 57 238
        Asian - East Asian Heritage
    		 192 193 195 192 772
        Asian - Japanese Heritage
    		 34 36 37 37 144
        Asian - Mixed Race
    		 1 0 0 0 1
        Asian - South East Asian Heritage
    		 389 399 386 394 1568
        Native Hawaiian or Other Pacific Islander
    		 1 2 0 2 5
        White - Arabic/North African Heritage
    		 14 13 7 12 46
        White - Mixed Race
    		 0 0 0 1 1
        White - White/Caucasian /European Heritage
    		 3334 3367 3353 3337 13391
        Mixed Race
    		 32 25 28 30 115

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo once daily (OD) in the morning from the dry powder inhaler (DPI) until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Reporting group title
    Fluticasone furoate 100 µg
    Reporting group description
    		 Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Reporting group title
    Vilanterol 25 µg
    Reporting group description
    		 Participants received Vilanterol (VI) 25 µg inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Reporting group title
    Fluticasone furoate/vilanterol 100/25 µg
    Reporting group description
    		 Participants received FF/VI 100/25 µg inhalation powder OD in the morning from the DPI until the required number of events (death) was achieved. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.

    Primary: Number of participants with death (both on and off treatment) due to any cause, time up to or on the pre-determined common end date

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    End point title
    		 Number of participants with death (both on and off treatment) due to any cause, time up to or on the pre-determined common end date
    End point description
    Death from any cause: which occurred from the day of starting IP until the Commone End Date (CED). Common End Date (CED) is the study end date that was pre determined where approximately 1000 deaths would have occurred in the Intent-toTreat Efficacy (ITT-E) Population. Only deaths which occurred on or before the CED were used for the primary analysis. Those who had not died by CED, but who were known to be alive on or after the CED, were censored at the CED. Cox Proportional Hazards (PH) Model was adjusted for age, and gender, including all 4 arms. A hazard ratio of less than 1 indicates a lower death rate versus placebo or other arm. ITT-E Population consisted of all participants in the Safety Population (i.e. randomized to IP and who received at least one dose of IP), with the exception of those recruited at sites that were closed.
    End point type
    Primary
    End point timeframe
    From the date of randomization until date of death due to any cause (average of 2 study years)
    End point values
    		 Placebo Fluticasone furoate 100 µg Vilanterol 25 µg Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects analysed
    4111 [1]
    4135 [2]
    4118 [3]
    4121 [4]
    Units: Participants
        Dead
    275
    251
    265
    246
        Alive
    3832
    3884
    3853
    3874
        Unknown
    4
    0
    0
    1
    Notes
    [1] - ITT-E Population
    [2] - ITT-E Population
    [3] - ITT-E Population
    [4] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8232
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.137
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.878
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.739
         upper limit
    		 1.042
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8232
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    12.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 26.1
    Notes
    [5] - Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v Fluticasone furoate 100 µg
    Number of subjects included in analysis
    8246
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.284
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.911
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.767
         upper limit
    		 1.081
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Placebo v Fluticasone furoate 100 µg
    Number of subjects included in analysis
    8246
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    8.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.1
         upper limit
    		 23.3
    Notes
    [6] - Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    Placebo v Vilanterol 25 µg
    Number of subjects included in analysis
    8229
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.655
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.962
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.813
         upper limit
    		 1.139
    Statistical analysis title
    		 Statistical Analysis 6
    Comparison groups
    Placebo v Vilanterol 25 µg
    Number of subjects included in analysis
    8229
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.9
         upper limit
    		 18.7
    Notes
    [7] - Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 7
    Comparison groups
    Fluticasone furoate 100 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8256
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.681
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.964
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.808
         upper limit
    		 1.149
    Statistical analysis title
    		 Statistical Analysis 8
    Comparison groups
    Fluticasone furoate 100 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8256
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.9
         upper limit
    		 19.2
    Notes
    [8] - Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 9
    Comparison groups
    Vilanterol 25 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.299
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.912
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.767
         upper limit
    		 1.085
    Statistical analysis title
    		 Statistical Analysis 10
    Comparison groups
    Vilanterol 25 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    8.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.5
         upper limit
    		 23.3
    Notes
    [9] - Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100

    Secondary: Decline in forced expiratory volume in 1 second (FEV1)

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    End point title
    		 Decline in forced expiratory volume in 1 second (FEV1)
    End point description
    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The effect of treatment on decline of post bronchodilator FEV1 recorded during the treatment period was analyzed using a particular form of a mixed effect model - a random coefficients model. FEV1 was fitted as the response variable with treatment group, age, gender, baseline FEV1 and time on treatment as fixed effects. Time on treatment was treated as a continuous variable. This model allowed for an initial increase in FEV1, but then tested the difference in slopes from the first post-baseline measurement which was at 3 months. A negative slope indicates a decline. A positive treatment difference indicates a slower rate of decline vs Placebo or Component. Only participants with at least one on-treatment post-bronchodilator FEV1 measurement were analyzed.
    End point type
    Secondary
    End point timeframe
    From start date of IP until IP stop date + 1 (assessed up to 4 years)
    End point values
    		 Placebo Fluticasone furoate 100 µg Vilanterol 25 µg Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects analysed
    3800 [10]
    3879 [11]
    3866 [12]
    3912 [13]
    Units: milliliter/year
        least squares mean (standard error)
    -46 ( 2.5 )
    -38 ( 2.4 )
    -47 ( 2.4 )
    -38 ( 2.4 )
    Notes
    [10] - ITT-E Population
    [11] - ITT-E Population
    [12] - ITT-E Population
    [13] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    7712
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.019
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 15
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.4
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v Fluticasone furoate 100 µg
    Number of subjects included in analysis
    7679
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.026
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 14
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.5
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v Vilanterol 25 µg
    Number of subjects included in analysis
    7666
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.654
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 5
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.4
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Fluticasone furoate 100 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    7791
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.913
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 7
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.4
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    Vilanterol 25 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    7778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3
         upper limit
    		 16
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.4

    Secondary: Number of participants with first on-treatment cardiovascular (CV) composite events occured on or before common end date

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    End point title
    		 Number of participants with first on-treatment cardiovascular (CV) composite events occured on or before common end date
    End point description
    On-treatment CV composite event is comprised of the first event that is adjudicated as on-treatment CV death, myocardial infarction, stroke, unstable angina, or transient ischemic attack experienced by a participant. The events that occurred no more than 7 days after the participants last dose of IP are considered as on-treatment adverse events. Common end date is the study end date where approximately 1000 deaths would have occurred in the ITT-E Population. Cox PH Model was used to assess time to first on-treatment CV composite event. Cox PH Model was adjusted for age, gender and indicators of ischemic and vascular disease, including all four treatment arms. A hazard ratio less than 1 indicates a lower risk of a first CV event rate versus placebo or any arm.
    End point type
    Secondary
    End point timeframe
    From the start of IP to first on treatment CV event till 7 days after the last dose of IP (average of 2 study years)
    End point values
    		 Placebo Fluticasone furoate 100 µg Vilanterol 25 µg Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects analysed
    4111 [14]
    4135 [15]
    4118 [16]
    4121 [17]
    Units: Participants
        Had CV composite event
    173
    161
    180
    174
        No CV composite event
    3938
    3974
    3938
    3947
    Notes
    [14] - ITT-E Population
    [15] - ITT-E Population
    [16] - ITT-E Population
    [17] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8232
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.475
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.926
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.143
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8232
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    7.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.3
         upper limit
    		 25
    Notes
    [18] - Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v Fluticasone furoate 100 µg
    Number of subjects included in analysis
    8246
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.317
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.896
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.723
         upper limit
    		 1.111
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Placebo v Fluticasone furoate 100 µg
    Number of subjects included in analysis
    8246
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    10.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.1
         upper limit
    		 27.7
    Notes
    [19] - Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    Placebo v Vilanterol 25 µg
    Number of subjects included in analysis
    8229
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.908
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.988
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.802
         upper limit
    		 1.217
    Statistical analysis title
    		 Statistical Analysis 6
    Comparison groups
    Placebo v Vilanterol 25 µg
    Number of subjects included in analysis
    8229
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.7
         upper limit
    		 19.8
    Notes
    [20] - Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 7
    Comparison groups
    Fluticasone furoate 100 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8256
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.763
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.033
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.834
         upper limit
    		 1.281
    Statistical analysis title
    		 Statistical Analysis 8
    Comparison groups
    Fluticasone furoate 100 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8256
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    -3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.1
         upper limit
    		 16.6
    Notes
    [21] - Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100
    Statistical analysis title
    		 Statistical Analysis 9
    Comparison groups
    Vilanterol 25 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.545
    Method
    		 Cox Proportional Hazards Model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.938
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.761
         upper limit
    		 1.155
    Statistical analysis title
    		 Statistical Analysis 10
    Comparison groups
    Vilanterol 25 µg v Fluticasone furoate/vilanterol 100/25 µg
    Number of subjects included in analysis
    8239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [22]
    Method
    Parameter type
    		 Percent reduction in risk of death
    Point estimate
    6.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.5
         upper limit
    		 23.9
    Notes
    [22] - Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)*100

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP until IP discontinuation + 1 day (average of 2 study years).
    Adverse event reporting additional description
    On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose IP.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants (par.) received placeboXXXXXXXXTO DO

    Reporting group title
    Fluticasone furoate 100 µg
    Reporting group description
    		 To DO

    Reporting group title
    Vilanterol 25 µg
    Reporting group description
    		 TO DO

    Reporting group title
    Fluticasone furoate/vilanterol 100/25 µg
    Reporting group description
    		 TO DO

    Serious adverse events
    		 Placebo Fluticasone furoate 100 µg Vilanterol 25 µg Fluticasone furoate/vilanterol 100/25 µg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    918 / 4131 (22.22%)
    929 / 4157 (22.35%)
    972 / 4140 (23.48%)
    961 / 4140 (23.21%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Acute lymphocytic leukaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Adenocarcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    5 / 4131 (0.12%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    4 / 4140 (0.10%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of salivary gland
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Adrenal adenoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angiomyolipoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Astrocytoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign lung neoplasm
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of adrenal gland
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of bladder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of prostate
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    5 / 4157 (0.12%)
    1 / 4140 (0.02%)
    5 / 4140 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Bladder cancer stage I, without cancer in situ
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    3 / 4131 (0.07%)
    3 / 4157 (0.07%)
    5 / 4140 (0.12%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma recurrent
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma stage 0
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Brain neoplasm malignant
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Breast cancer
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    4 / 4140 (0.10%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Breast cancer in situ
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Breast cancer stage I
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brenner tumour
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    4 / 4131 (0.10%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    Bronchioloalveolar carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carcinoid tumour
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Choroid melanoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic myeloid leukaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    5 / 4140 (0.12%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    Colon cancer recurrent
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Colon cancer stage IV
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Colon neoplasm
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear neoplasm malignant
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eyelid haemangioma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Gastric cancer stage I
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer stage III
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Head and neck cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Hepatic cancer metastatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hepatic neoplasm
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Inflammatory pseudotumour
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal adenocarcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratoacanthoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lip and/or oral cavity cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    5 / 4131 (0.12%)
    3 / 4157 (0.07%)
    4 / 4140 (0.10%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 2
    Lung adenocarcinoma metastatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Lung adenocarcinoma stage I
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lung adenocarcinoma stage IV
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    2 / 4131 (0.05%)
    5 / 4157 (0.12%)
    3 / 4140 (0.07%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
    0 / 1
    Lung carcinoma cell type unspecified recurrent
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage 0
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage III
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Lung neoplasm
         subjects affected / exposed
    5 / 4131 (0.12%)
    4 / 4157 (0.10%)
    3 / 4140 (0.07%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 3
    Lung neoplasm malignant
         subjects affected / exposed
    8 / 4131 (0.19%)
    13 / 4157 (0.31%)
    17 / 4140 (0.41%)
    10 / 4140 (0.24%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 13
    0 / 17
    0 / 10
         deaths causally related to treatment / all
    0 / 3
    0 / 7
    0 / 8
    0 / 2
    Lung squamous cell carcinoma metastatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Lung squamous cell carcinoma stage II
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung squamous cell carcinoma stage III
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lung squamous cell carcinoma stage IV
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Lymphangiosis carcinomatosa
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphocytic lymphoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm of ampulla of Vater
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm of choroid
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningioma benign
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesenteric neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesothelioma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Metastases to adrenals
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Metastases to bone marrow
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    Metastases to liver
         subjects affected / exposed
    6 / 4131 (0.15%)
    2 / 4157 (0.05%)
    9 / 4140 (0.22%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 2
    Metastases to lung
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Metastases to skin
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastases to spine
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Metastases to spleen
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to stomach
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Metastatic malignant melanoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastatic renal cell carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Myeloproliferative disorder
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Neoplasm prostate
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    3 / 4131 (0.07%)
    7 / 4157 (0.17%)
    0 / 4140 (0.00%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
    0 / 0
    Non-small cell lung cancer stage I
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer stage II
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer stage IIIA
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Non-small cell lung cancer stage IIIB
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal squamous cell carcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Oesophageal squamous cell carcinoma metastatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal squamous cell carcinoma stage II
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Oral neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cancer metastatic
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ovarian germ cell teratoma benign
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian granulosa cell tumour
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    6 / 4131 (0.15%)
    1 / 4157 (0.02%)
    4 / 4140 (0.10%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 2
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Papillary cystadenoma lymphomatosum
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phyllodes tumour
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Polycythaemia vera
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    5 / 4131 (0.12%)
    4 / 4157 (0.10%)
    8 / 4140 (0.19%)
    11 / 4140 (0.27%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 8
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    Prostate cancer metastatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Prostate cancer recurrent
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    3 / 4131 (0.07%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Rectal adenoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Rectal neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Renal neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal oncocytoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Round cell liposarcoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schwannoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scrotal cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    4 / 4131 (0.10%)
    3 / 4157 (0.07%)
    3 / 4140 (0.07%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 4
    Small cell lung cancer metastatic
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Small intestine carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Spinal cord neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    4 / 4140 (0.10%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    6 / 4131 (0.15%)
    6 / 4157 (0.14%)
    5 / 4140 (0.12%)
    12 / 4140 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
    0 / 5
    0 / 12
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 6
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the cervix
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    T-cell lymphoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Throat cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thymoma malignant
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Thyroid neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteric cancer
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyosarcoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vocal cord neoplasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulvar adenocarcinoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    10 / 4131 (0.24%)
    8 / 4157 (0.19%)
    5 / 4140 (0.12%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Aortic aneurysm rupture
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 1
    Aortic arteriosclerosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic dilatation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic disorder
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Aortic stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Aortic thrombosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial rupture
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial thrombosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Arteriovenous fistula
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Deep vein thrombosis
         subjects affected / exposed
    6 / 4131 (0.15%)
    5 / 4157 (0.12%)
    4 / 4140 (0.10%)
    5 / 4140 (0.12%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic microangiopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral artery occlusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    3 / 4157 (0.07%)
    3 / 4140 (0.07%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    7 / 4131 (0.17%)
    9 / 4157 (0.22%)
    8 / 4140 (0.19%)
    11 / 4140 (0.27%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 9
    1 / 8
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    3 / 4131 (0.07%)
    5 / 4157 (0.12%)
    5 / 4140 (0.12%)
    9 / 4140 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    4 / 4131 (0.10%)
    8 / 4157 (0.19%)
    2 / 4140 (0.05%)
    7 / 4140 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Iliac artery occlusion
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leriche syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Penetrating atherosclerotic ulcer
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    9 / 4131 (0.22%)
    16 / 4157 (0.38%)
    11 / 4140 (0.27%)
    5 / 4140 (0.12%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 19
    0 / 11
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    4 / 4131 (0.10%)
    3 / 4157 (0.07%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    2 / 4131 (0.05%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral circulatory failure
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    4 / 4131 (0.10%)
    3 / 4157 (0.07%)
    3 / 4140 (0.07%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 4131 (0.02%)
    8 / 4157 (0.19%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Poor peripheral circulation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Raynaud's phenomenon
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renovascular hypertension
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Secondary hypertension
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Subclavian artery occlusion
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subclavian artery stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subclavian steal syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Temporal arteritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thromboangiitis obliterans
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular occlusion
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vasoconstriction
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous occlusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vessel perforation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Finger amputation
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Knee arthroplasty
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff repair
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgery
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac death
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    16 / 4131 (0.39%)
    10 / 4157 (0.24%)
    8 / 4140 (0.19%)
    16 / 4140 (0.39%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 10
    0 / 8
    1 / 18
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 0
    Cyst
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    6 / 4131 (0.15%)
    7 / 4157 (0.17%)
    5 / 4140 (0.12%)
    7 / 4140 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 7
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 6
    1 / 7
    0 / 5
    0 / 7
    Device defective
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device deployment issue
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device electrical finding
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device failure
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device issue
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocution
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic ulcer
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    2 / 4131 (0.05%)
    3 / 4157 (0.07%)
    2 / 4140 (0.05%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 5
    Non-cardiac chest pain
         subjects affected / exposed
    4 / 4131 (0.10%)
    5 / 4157 (0.12%)
    10 / 4140 (0.24%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 10
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    3 / 4131 (0.07%)
    7 / 4157 (0.17%)
    6 / 4140 (0.14%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 7
    0 / 6
    0 / 1
    Sudden death
         subjects affected / exposed
    20 / 4131 (0.48%)
    14 / 4157 (0.34%)
    17 / 4140 (0.41%)
    20 / 4140 (0.48%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 14
    0 / 17
    0 / 20
         deaths causally related to treatment / all
    0 / 20
    0 / 14
    0 / 17
    0 / 20
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Drug hypersensitivity
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Food allergy
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    3 / 4131 (0.07%)
    7 / 4157 (0.17%)
    3 / 4140 (0.07%)
    5 / 4140 (0.12%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 7
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast pain
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical polyp
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fallopian tube cyst
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peyronie's disease
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatomegaly
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine enlargement
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    17 / 4131 (0.41%)
    7 / 4157 (0.17%)
    8 / 4140 (0.19%)
    12 / 4140 (0.29%)
         occurrences causally related to treatment / all
    1 / 18
    0 / 7
    0 / 8
    0 / 12
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial polyp
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial secretion retention
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchostenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bullous lung disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    262 / 4131 (6.34%)
    214 / 4157 (5.15%)
    245 / 4140 (5.92%)
    189 / 4140 (4.57%)
         occurrences causally related to treatment / all
    10 / 356
    7 / 274
    7 / 326
    6 / 237
         deaths causally related to treatment / all
    0 / 6
    0 / 6
    0 / 4
    1 / 8
    Chronic respiratory failure
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 4131 (0.15%)
    9 / 4157 (0.22%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 9
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Dyspnoea at rest
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 4131 (0.05%)
    8 / 4157 (0.19%)
    3 / 4140 (0.07%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    3 / 4140 (0.07%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal polyp
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung consolidation
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Lung infiltration
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal septum disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal cyst
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pickwickian syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    6 / 4131 (0.15%)
    3 / 4157 (0.07%)
    3 / 4140 (0.07%)
    9 / 4140 (0.22%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 3
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pleurisy
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    7 / 4131 (0.17%)
    6 / 4157 (0.14%)
    4 / 4140 (0.10%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    10 / 4131 (0.24%)
    12 / 4157 (0.29%)
    17 / 4140 (0.41%)
    13 / 4140 (0.31%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 14
    0 / 17
    0 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 5
    0 / 6
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hilum mass
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 4131 (0.05%)
    4 / 4157 (0.10%)
    4 / 4140 (0.10%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    Respiratory distress
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    8 / 4131 (0.19%)
    7 / 4157 (0.17%)
    9 / 4140 (0.22%)
    9 / 4140 (0.22%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
    0 / 9
    0 / 9
         deaths causally related to treatment / all
    0 / 2
    0 / 4
    0 / 4
    0 / 3
    Sinus polyp
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vocal cord disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol abuse
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol withdrawal syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug abuse
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphoria
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination, visual
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    2 / 4131 (0.05%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychogenic seizure
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizoaffective disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizophrenia, paranoid type
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Substance abuse
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Substance-induced mood disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal behaviour
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriogram coronary
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood glucose fluctuation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood urine present
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest X-ray abnormal
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial necrosis marker increased
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anastomotic ulcer haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Burns third degree
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract traumatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chemical burn of skin
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chemical injury
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Concussion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    4 / 4157 (0.10%)
    4 / 4140 (0.10%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Coronary artery restenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary vascular graft occlusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dislocation of vertebra
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Exposure via inhalation
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye contusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to anastomose
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    4 / 4131 (0.10%)
    2 / 4157 (0.05%)
    4 / 4140 (0.10%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    2 / 4131 (0.05%)
    4 / 4157 (0.10%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    5 / 4131 (0.12%)
    6 / 4157 (0.14%)
    5 / 4140 (0.12%)
    8 / 4140 (0.19%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal injury
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic haematoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    3 / 4131 (0.07%)
    4 / 4157 (0.10%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal anastomosis complication
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint capsule rupture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb crushing injury
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb traumatic amputation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Muscle injury
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periorbital contusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periprosthetic fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post laminectomy syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative hernia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    6 / 4140 (0.14%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Scar
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shunt thrombosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Tendon rupture
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral injury
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VIth nerve injury
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular graft occlusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular graft thrombosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Wound evisceration
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Adrenogenital syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial septal defect
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocele
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyloric stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sturge-Weber syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vitello-intestinal duct remnant
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    3 / 4131 (0.07%)
    3 / 4157 (0.07%)
    6 / 4140 (0.14%)
    5 / 4140 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Acute myocardial infarction
         subjects affected / exposed
    23 / 4131 (0.56%)
    20 / 4157 (0.48%)
    21 / 4140 (0.51%)
    28 / 4140 (0.68%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 20
    0 / 21
    2 / 30
         deaths causally related to treatment / all
    0 / 5
    0 / 6
    0 / 4
    1 / 7
    Adams-Stokes syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    22 / 4131 (0.53%)
    19 / 4157 (0.46%)
    20 / 4140 (0.48%)
    12 / 4140 (0.29%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 21
    0 / 22
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    23 / 4131 (0.56%)
    22 / 4157 (0.53%)
    16 / 4140 (0.39%)
    23 / 4140 (0.56%)
         occurrences causally related to treatment / all
    0 / 24
    1 / 24
    3 / 17
    1 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 4131 (0.02%)
    4 / 4157 (0.10%)
    3 / 4140 (0.07%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 4
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 2
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    Atrial fibrillation
         subjects affected / exposed
    31 / 4131 (0.75%)
    22 / 4157 (0.53%)
    30 / 4140 (0.72%)
    32 / 4140 (0.77%)
         occurrences causally related to treatment / all
    3 / 37
    0 / 23
    5 / 31
    4 / 36
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    6 / 4131 (0.15%)
    3 / 4157 (0.07%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    1 / 6
    1 / 3
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Atrioventricular block complete
         subjects affected / exposed
    3 / 4131 (0.07%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Bundle branch block right
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    9 / 4131 (0.22%)
    9 / 4157 (0.22%)
    11 / 4140 (0.27%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 9
    0 / 11
    0 / 4
         deaths causally related to treatment / all
    0 / 7
    0 / 8
    0 / 9
    0 / 2
    Cardiac failure
         subjects affected / exposed
    28 / 4131 (0.68%)
    17 / 4157 (0.41%)
    19 / 4140 (0.46%)
    28 / 4140 (0.68%)
         occurrences causally related to treatment / all
    0 / 30
    0 / 18
    0 / 23
    1 / 31
         deaths causally related to treatment / all
    0 / 8
    0 / 4
    0 / 5
    0 / 7
    Cardiac failure acute
         subjects affected / exposed
    7 / 4131 (0.17%)
    3 / 4157 (0.07%)
    3 / 4140 (0.07%)
    7 / 4140 (0.17%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 3
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 6
    0 / 1
    0 / 2
    0 / 5
    Cardiac failure chronic
         subjects affected / exposed
    5 / 4131 (0.12%)
    7 / 4157 (0.17%)
    4 / 4140 (0.10%)
    7 / 4140 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 2
    Cardiac failure congestive
         subjects affected / exposed
    26 / 4131 (0.63%)
    26 / 4157 (0.63%)
    21 / 4140 (0.51%)
    30 / 4140 (0.72%)
         occurrences causally related to treatment / all
    1 / 30
    0 / 33
    0 / 22
    0 / 33
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    0 / 2
    0 / 1
    Cardiac perforation
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    11 / 4131 (0.27%)
    9 / 4157 (0.22%)
    11 / 4140 (0.27%)
    5 / 4140 (0.12%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 9
    0 / 11
    0 / 5
         deaths causally related to treatment / all
    0 / 10
    0 / 9
    0 / 10
    0 / 4
    Cardiogenic shock
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    Cardiomegaly
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    4 / 4140 (0.10%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    1 / 3
    0 / 3
    0 / 4
    Cardiovascular disorder
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Conduction disorder
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    22 / 4131 (0.53%)
    14 / 4157 (0.34%)
    25 / 4140 (0.60%)
    24 / 4140 (0.58%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 14
    0 / 26
    0 / 25
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery thrombosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Coronary ostial stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diastolic dysfunction
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extrasystoles
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    4 / 4131 (0.10%)
    3 / 4157 (0.07%)
    4 / 4140 (0.10%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    3 / 4131 (0.07%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Left ventricular hypertrophy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial fibrosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    24 / 4131 (0.58%)
    32 / 4157 (0.77%)
    26 / 4140 (0.63%)
    24 / 4140 (0.58%)
         occurrences causally related to treatment / all
    0 / 24
    1 / 35
    0 / 27
    0 / 25
         deaths causally related to treatment / all
    0 / 10
    1 / 17
    0 / 16
    0 / 7
    Myocardial ischaemia
         subjects affected / exposed
    7 / 4131 (0.17%)
    8 / 4157 (0.19%)
    5 / 4140 (0.12%)
    7 / 4140 (0.17%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 8
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    Myocardial necrosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Rheumatic heart disease
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    3 / 4131 (0.07%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachyarrhythmia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia paroxysmal
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricle rupture
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    3 / 4140 (0.07%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 4131 (0.00%)
    3 / 4157 (0.07%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amyotrophic lateral sclerosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Aphasia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal ganglia infarction
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basilar artery occlusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Brain mass
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain stem ischaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Brain stem stroke
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid arteriosclerosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery aneurysm
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    4 / 4131 (0.10%)
    6 / 4157 (0.14%)
    4 / 4140 (0.10%)
    7 / 4140 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar atrophy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral arteriosclerosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral atrophy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    5 / 4131 (0.12%)
    6 / 4157 (0.14%)
    4 / 4140 (0.10%)
    7 / 4140 (0.17%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
    0 / 4
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    Cerebral ischaemia
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ventricle dilatation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrospinal fluid leakage
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    16 / 4131 (0.39%)
    11 / 4157 (0.26%)
    11 / 4140 (0.27%)
    18 / 4140 (0.43%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 11
    0 / 11
    0 / 20
         deaths causally related to treatment / all
    0 / 8
    0 / 2
    0 / 3
    0 / 6
    Cerebrovascular disorder
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Cerebrovascular insufficiency
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical myelopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Complex partial seizures
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diplegia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic cerebral infarction
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    4 / 4131 (0.10%)
    4 / 4157 (0.10%)
    4 / 4140 (0.10%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
    0 / 1
    Headache
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intercostal neuralgia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    19 / 4131 (0.46%)
    15 / 4157 (0.36%)
    14 / 4140 (0.34%)
    19 / 4140 (0.46%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 15
    1 / 16
    0 / 21
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    1 / 3
    0 / 3
    Lacunar infarction
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meralgia paraesthetica
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurological symptom
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postictal paralysis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radicular syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sacral radiculopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    4 / 4140 (0.10%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Speech disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylitic myelopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Syncope
         subjects affected / exposed
    6 / 4131 (0.15%)
    7 / 4157 (0.17%)
    6 / 4140 (0.14%)
    10 / 4140 (0.24%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 7
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic outlet syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    7 / 4131 (0.17%)
    13 / 4157 (0.31%)
    16 / 4140 (0.39%)
    9 / 4140 (0.22%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 13
    0 / 16
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular encephalopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular parkinsonism
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral artery stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    8 / 4131 (0.19%)
    6 / 4157 (0.14%)
    3 / 4140 (0.07%)
    5 / 4140 (0.12%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone marrow oedema
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercoagulation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersplenism
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune thrombocytopenic purpura
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polycythaemia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic vein thrombosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spontaneous haematoma
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Meniere's disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tinnitus
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tympanic membrane perforation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 4131 (0.00%)
    4 / 4157 (0.10%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Angle closure glaucoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blindness unilateral
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    1 / 4131 (0.02%)
    5 / 4157 (0.12%)
    8 / 4140 (0.19%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 8
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract cortical
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eyelid ptosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iridodonesis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lens dislocation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ocular hypertension
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ocular ischaemic syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal disorder
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal tear
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal vascular disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vitreous prolapse
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    5 / 4140 (0.12%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal incarcerated hernia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 4131 (0.00%)
    3 / 4157 (0.07%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Anal fissure
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 4131 (0.10%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dieulafoy's vascular malformation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erosive duodenitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral hernia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    4 / 4140 (0.10%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    5 / 4140 (0.12%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroduodenal haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    4 / 4131 (0.10%)
    4 / 4157 (0.10%)
    4 / 4140 (0.10%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gingival bleeding
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    5 / 4140 (0.12%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inflammatory bowel disease
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    8 / 4131 (0.19%)
    4 / 4157 (0.10%)
    4 / 4140 (0.10%)
    8 / 4140 (0.19%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia strangulated
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal infarction
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 4131 (0.05%)
    3 / 4157 (0.07%)
    3 / 4140 (0.07%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mallory-Weiss syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Noninfective sialoadenitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedematous pancreatitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis ulcerative
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic necrosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pancreatitis
         subjects affected / exposed
    2 / 4131 (0.05%)
    4 / 4157 (0.10%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    4 / 4131 (0.10%)
    7 / 4157 (0.17%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer perforation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritoneal adhesions
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritoneal perforation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 4131 (0.07%)
    5 / 4157 (0.12%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Varices oesophageal
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Alcoholic liver disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cholecystitis
         subjects affected / exposed
    7 / 4131 (0.17%)
    4 / 4157 (0.10%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    5 / 4131 (0.12%)
    3 / 4157 (0.07%)
    4 / 4140 (0.10%)
    8 / 4140 (0.19%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic hepatitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Hepatic function abnormal
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic steatosis
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatorenal failure
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hepatorenal syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Portal hypertension
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post cholecystectomy syndrome
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermal cyst
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis allergic
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis exfoliative
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema nodosum
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Idiopathic angioedema
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathic ulcer
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Photosensitivity reaction
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pruritus
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin maceration
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin oedema
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin sensitisation
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    7 / 4131 (0.17%)
    7 / 4157 (0.17%)
    8 / 4140 (0.19%)
    9 / 4140 (0.22%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    Acute prerenal failure
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder neck sclerosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus bladder
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    4 / 4131 (0.10%)
    6 / 4157 (0.14%)
    2 / 4140 (0.05%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic nephropathy
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    4 / 4131 (0.10%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    4 / 4140 (0.10%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nocturia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prerenal failure
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 4131 (0.05%)
    7 / 4157 (0.17%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Renal mass
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder polyp
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 4131 (0.02%)
    4 / 4157 (0.10%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Addison's disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adrenal insufficiency
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basedow's disease
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Goitre
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    3 / 4140 (0.07%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism secondary
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Primary hyperaldosteronism
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    4 / 4140 (0.10%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthrofibrosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone lesion
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coccydynia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dupuytren's contracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibromyalgia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture nonunion
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gouty arthritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    3 / 4131 (0.07%)
    3 / 4157 (0.07%)
    5 / 4140 (0.12%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    4 / 4131 (0.10%)
    1 / 4157 (0.02%)
    4 / 4140 (0.10%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    14 / 4131 (0.34%)
    10 / 4157 (0.24%)
    11 / 4140 (0.27%)
    8 / 4140 (0.19%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 10
    0 / 11
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periarthritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scoliosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal disorder
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    3 / 4131 (0.07%)
    0 / 4157 (0.00%)
    4 / 4140 (0.10%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal sepsis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess intestinal
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute hepatitis B
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amoebiasis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical mycobacterial infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast abscess
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    12 / 4131 (0.29%)
    9 / 4157 (0.22%)
    6 / 4140 (0.14%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    1 / 15
    2 / 9
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    3 / 4131 (0.07%)
    8 / 4157 (0.19%)
    7 / 4140 (0.17%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    5 / 4131 (0.12%)
    10 / 4157 (0.24%)
    0 / 4140 (0.00%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 10
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis infective
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 4131 (0.00%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    4 / 4131 (0.10%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolic pneumonia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Emphysematous cystitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Endophthalmitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder empyema
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    3 / 4131 (0.07%)
    3 / 4157 (0.07%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Gastroenteritis
         subjects affected / exposed
    6 / 4131 (0.15%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis staphylococcal
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal fungal infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster disseminated
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incision site abscess
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected bites
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    4 / 4131 (0.10%)
    6 / 4157 (0.14%)
    3 / 4140 (0.07%)
    6 / 4140 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    2 / 7
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Intervertebral discitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    8 / 4131 (0.19%)
    8 / 4157 (0.19%)
    5 / 4140 (0.12%)
    9 / 4140 (0.22%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 8
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 4131 (0.05%)
    4 / 4157 (0.10%)
    0 / 4140 (0.00%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymph gland infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymph node abscess
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningoencephalitis herpetic
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroborreliosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal candidiasis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    4 / 4157 (0.10%)
    1 / 4140 (0.02%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis externa bacterial
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    4 / 4140 (0.10%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    113 / 4131 (2.74%)
    121 / 4157 (2.91%)
    90 / 4140 (2.17%)
    123 / 4140 (2.97%)
         occurrences causally related to treatment / all
    3 / 128
    13 / 145
    3 / 99
    11 / 140
         deaths causally related to treatment / all
    0 / 8
    2 / 10
    0 / 3
    0 / 14
    Pneumonia bacterial
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia moraxella
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Purulent discharge
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelocystitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    2 / 4131 (0.05%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection bacterial
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salmonella sepsis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scrotal abscess
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    10 / 4131 (0.24%)
    4 / 4157 (0.10%)
    4 / 4140 (0.10%)
    8 / 4140 (0.19%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 4
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
    0 / 1
    Septic shock
         subjects affected / exposed
    5 / 4131 (0.12%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    0 / 1
    0 / 1
    Sialoadenitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis septic
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic shock syndrome
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    3 / 4157 (0.07%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Tuberculous pleurisy
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Typhoid fever
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 4131 (0.07%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    5 / 4131 (0.12%)
    7 / 4157 (0.17%)
    6 / 4140 (0.14%)
    9 / 4140 (0.22%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
    0 / 6
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    2 / 4140 (0.05%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral myocarditis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    1 / 4140 (0.02%)
    2 / 4140 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cachexia
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    3 / 4140 (0.07%)
    3 / 4140 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    5 / 4131 (0.12%)
    1 / 4157 (0.02%)
    6 / 4140 (0.14%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    4 / 4131 (0.10%)
    6 / 4157 (0.14%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 4131 (0.02%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    2 / 4157 (0.05%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    3 / 4131 (0.07%)
    0 / 4157 (0.00%)
    2 / 4140 (0.05%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    4 / 4131 (0.10%)
    3 / 4157 (0.07%)
    0 / 4140 (0.00%)
    4 / 4140 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 4131 (0.05%)
    0 / 4157 (0.00%)
    1 / 4140 (0.02%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 4131 (0.05%)
    1 / 4157 (0.02%)
    4 / 4140 (0.10%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 4131 (0.02%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    0 / 4131 (0.00%)
    0 / 4157 (0.00%)
    0 / 4140 (0.00%)
    1 / 4140 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 4131 (0.02%)
    2 / 4157 (0.05%)
    2 / 4140 (0.05%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 4131 (0.00%)
    1 / 4157 (0.02%)
    0 / 4140 (0.00%)
    0 / 4140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Placebo Fluticasone furoate 100 µg Vilanterol 25 µg Fluticasone furoate/vilanterol 100/25 µg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1862 / 4131 (45.07%)
    1941 / 4157 (46.69%)
    1827 / 4140 (44.13%)
    1761 / 4140 (42.54%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    129 / 4131 (3.12%)
    138 / 4157 (3.32%)
    124 / 4140 (3.00%)
    152 / 4140 (3.67%)
         occurrences all number
    192
    189
    194
    214
    Nervous system disorders
    Headache
         subjects affected / exposed
    308 / 4131 (7.46%)
    332 / 4157 (7.99%)
    327 / 4140 (7.90%)
    291 / 4140 (7.03%)
         occurrences all number
    585
    686
    614
    536
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    969 / 4131 (23.46%)
    939 / 4157 (22.59%)
    938 / 4140 (22.66%)
    779 / 4140 (18.82%)
         occurrences all number
    1731
    1517
    1689
    1187
    Cough
         subjects affected / exposed
    254 / 4131 (6.15%)
    224 / 4157 (5.39%)
    215 / 4140 (5.19%)
    206 / 4140 (4.98%)
         occurrences all number
    338
    259
    285
    264
    Dyspnoea
         subjects affected / exposed
    172 / 4131 (4.16%)
    185 / 4157 (4.45%)
    132 / 4140 (3.19%)
    125 / 4140 (3.02%)
         occurrences all number
    254
    233
    195
    160
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    140 / 4131 (3.39%)
    168 / 4157 (4.04%)
    162 / 4140 (3.91%)
    173 / 4140 (4.18%)
         occurrences all number
    170
    249
    209
    235
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    165 / 4131 (3.99%)
    184 / 4157 (4.43%)
    168 / 4140 (4.06%)
    166 / 4140 (4.01%)
         occurrences all number
    228
    229
    226
    223
    Influenza
         subjects affected / exposed
    118 / 4131 (2.86%)
    116 / 4157 (2.79%)
    122 / 4140 (2.95%)
    137 / 4140 (3.31%)
         occurrences all number
    147
    160
    162
    192
    Nasopharyngitis
         subjects affected / exposed
    310 / 4131 (7.50%)
    366 / 4157 (8.80%)
    352 / 4140 (8.50%)
    367 / 4140 (8.86%)
         occurrences all number
    414
    536
    478
    567
    Upper respiratory tract infection
         subjects affected / exposed
    194 / 4131 (4.70%)
    240 / 4157 (5.77%)
    212 / 4140 (5.12%)
    262 / 4140 (6.33%)
         occurrences all number
    271
    340
    289
    362

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Jan 2011
    Amendment no.01: Revised exclusion criteria regarding severe heart failure to include subjects with an implantable cardiac defibrillator (ICD) and provided clarification regarding disease related events/outcomes which would not be subject to expedited reporting.
    18 Feb 2011
    Amendment no.02: Revised the Run in period
    30 Apr 2013
    Amendment no.03: Added efficacy endpoints (cardiovascular procedures and change from baseline in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and clarified wording regarding washout of prohibited medications.
    17 Apr 2014
    Amendment no.04: Applied only to sites in Korea and revised the statement regarding use of non cardioselective beta blockers introduced in Amendment 03
    07 May 2015
    Amendment no.05: Revised the list of biomarkers (other endpoint), added time to first COPD exacerbation and deleted the analysis of time to COPD related death, and updated other treatment comparisons of interest.

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

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