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    Clinical Trial Results:
    A phase III, 52 week, randomized, double-blind, 3-arm parallel group study, comparing the efficacy, safety and tolerability of the fixed dose triple combination fluticasone furoate/umeclidinium/vilanterol, with the fixed dose dual combinations of fluticasone furoate/vilanterol and umeclidinium/vilanterol, all administered once-daily in the morning via a dry powder inhaler in subjects with chronic obstructive pulmonary disease

    Summary
    EudraCT number
    		 2013-003075-35
    Trial protocol
    		 NL   FI   PL   SE   DE   AT   CZ   BE   DK   ES   NO   RO   HR  
    Global end of trial date
    17 Jul 2017

    Results information
    Results version number
    		 v2(current)
    This version publication date
    27 Sep 2018
    First version publication date
    22 Jul 2018
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    116855
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    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
    19 Oct 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jul 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of Fluticasone Furoate (FF)/Umeclidinium (UMEC)/Vilanterol (VI), to reduce the annual rate of moderate and severe exacerbations compared with dual therapy of FF/VI or UMEC/VI in participants with, chronic obstructive pulmonary disease (COPD).
    Protection of trial subjects
    An Independent data monitoring committee (IDMC) reviewed unblinded safety data periodically throughout the trial to ensure participant safety.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Jun 2014
    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: 1085
    Country: Number of subjects enrolled
    Australia: 256
    Country: Number of subjects enrolled
    Austria: 130
    Country: Number of subjects enrolled
    Belgium: 139
    Country: Number of subjects enrolled
    Brazil: 143
    Country: Number of subjects enrolled
    Canada: 309
    Country: Number of subjects enrolled
    Chile: 434
    Country: Number of subjects enrolled
    China: 669
    Country: Number of subjects enrolled
    Colombia: 62
    Country: Number of subjects enrolled
    Czech Republic: 150
    Country: Number of subjects enrolled
    Denmark: 128
    Country: Number of subjects enrolled
    Finland: 101
    Country: Number of subjects enrolled
    France: 175
    Country: Number of subjects enrolled
    Germany: 1408
    Country: Number of subjects enrolled
    Hong Kong: 50
    Country: Number of subjects enrolled
    Israel: 265
    Country: Number of subjects enrolled
    Japan: 470
    Country: Number of subjects enrolled
    Korea, Republic of: 424
    Country: Number of subjects enrolled
    Netherlands: 367
    Country: Number of subjects enrolled
    New Zealand: 103
    Country: Number of subjects enrolled
    Norway: 122
    Country: Number of subjects enrolled
    Peru: 253
    Country: Number of subjects enrolled
    Philippines: 130
    Country: Number of subjects enrolled
    Poland: 95
    Country: Number of subjects enrolled
    Puerto Rico: 56
    Country: Number of subjects enrolled
    Romania: 108
    Country: Number of subjects enrolled
    Russian Federation: 368
    Country: Number of subjects enrolled
    Singapore: 25
    Country: Number of subjects enrolled
    South Africa: 365
    Country: Number of subjects enrolled
    Spain: 654
    Country: Number of subjects enrolled
    Sweden: 168
    Country: Number of subjects enrolled
    Thailand: 174
    Country: Number of subjects enrolled
    Turkey: 60
    Country: Number of subjects enrolled
    Ukraine: 113
    Country: Number of subjects enrolled
    United Kingdom: 292
    Country: Number of subjects enrolled
    United States: 3936
    Country: Number of subjects enrolled
    Vietnam: 118
    Worldwide total number of subjects
    13905
    EEA total number of subjects
    4037
    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)
    6312
    From 65 to 84 years
    7476
    85 years and over
    117

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants with chronic obstructive pulmonary disease (COPD), were randomized to the study. Study was conducted from 30 June 2014 to 17 July 2017, at total of 971 sites in 37 countries.

    Pre-assignment
    Screening details
    		 A total of 13,906 participants (par.) were registered for the study of which 13099 were screened (807 pre-screen failure) and 10,367 were randomized to the study (2744 screen failure). Of which 12 par. were randomized in error and 10,355 were randomized to actual treatment and included in Intent to treat (ITT) 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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 FF/UMEC/VI
    Arm description
    		 The eligible participants in this arm received Fluticasone Furoate (FF)/Umeclidinium (UMEC)/Vilanterol (VI) as a fixed dose combination (FDC) as 100 microgram (µcg)/62.5µcg/25µcg once daily (QD) via a dry powder inhaler (DPI), in the morning, for duration of 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fluticasone Furoate/Umeclidinium/Vilanterol Trifenatate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Administered as 100µcg/62.5µcg/25µcg, QD in morning via DPI for 52-weeks

    Arm title
    		 FF/VI
    Arm description
    		 The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
    Arm type
    		 Active comparator

    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
    Administered as 100µcg/25µcg, QD in morning via DPI for 52-weeks

    Arm title
    		 UMEC/VI
    Arm description
    		 The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Umeclidinium/ Vilanterol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Administered as 62.5µcg/25µcg, QD in morning via DPI for 52-weeks

    Number of subjects in period 1 [1]
    		FF/UMEC/VI FF/VI UMEC/VI
    Started
    4151
    4134
    2070
    Completed Investigational Product (IP)
    3393 [2]
    3094 [3]
    1504 [4]
    Not completed IP
    758 [5]
    1040 [6]
    566 [7]
    Withdrew IP (WIP): Adverse event
    249 [8]
    325 [9]
    186 [10]
    WIP: Lack of efficacy
    163 [11]
    313 [12]
    172 [13]
    Withdrew IP: Protocol deviation
    32 [14]
    41 [15]
    19 [16]
    WIP (Other): Stopping criteria reached
    4 [17]
    1 [18]
    2 [19]
    WIP: Study closed/terminated
    5 [20]
    2 [21]
    5 [22]
    WIP: Lost to follow-up
    21 [23]
    25 [24]
    14 [25]
    WIP: Investigator discretion
    33 [26]
    36 [27]
    15 [28]
    WIP: Withdrawal by participant
    250 [29]
    296 [30]
    153 [31]
    WIP :Did not complete Study treatment
    1 [32]
    1 [33]
    0 [34]
    Completed
    3714
    3598
    1775
    Not completed
    437
    536
    295
         Adverse event, serious fatal
    85
    91
    58
         Physician decision
    47
    57
    28
         Consent withdrawn by subject
    192
    261
    130
         Adverse event, non-fatal
    77
    89
    53
         Other: Reason not provided by site
    1
    -
    -
         Other: Study Closed or terminated
    5
    2
    4
         Lost to follow-up
    30
    36
    22
    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: This number indicates the number of participants with withdrawal from investigational product only.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [15] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [16] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [17] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [18] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [19] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [20] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [21] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [22] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [23] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [24] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [25] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [26] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [27] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [28] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [29] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [30] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [31] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [32] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [33] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.
    [34] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This number indicates the number of participants with withdrawal from investigational product only.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    FF/UMEC/VI
    Reporting group description
    		 The eligible participants in this arm received Fluticasone Furoate (FF)/Umeclidinium (UMEC)/Vilanterol (VI) as a fixed dose combination (FDC) as 100 microgram (µcg)/62.5µcg/25µcg once daily (QD) via a dry powder inhaler (DPI), in the morning, for duration of 52 weeks.

    Reporting group title
    FF/VI
    Reporting group description
    		 The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.

    Reporting group title
    UMEC/VI
    Reporting group description
    		 The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.

    Reporting group values
    		 FF/UMEC/VI FF/VI UMEC/VI Total
    Number of subjects
    		 4151 4134 2070
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 65.3 ± 8.24 65.3 ± 8.30 65.2 ± 8.26 -
    Gender categorical
    Units: Subjects
        Female
    		 1385 1386 714 3485
        Male
    		 2766 2748 1356 6870
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 87 86 45 218
        Asian - Central/South Asian Heritage
    		 6 3 1 10
        Asian - East Asian Heritage
    		 362 374 177 913
        Asian - Japanese Heritage
    		 151 152 82 385
        Asian - South East Asian Heritage
    		 149 147 75 371
        Black or African American
    		 122 99 43 264
        Native Hawaiian or other Pacific Islander
    		 2 3 2 7
        White - Arabic/North African Heritage
    		 31 45 24 100
        White - White/Caucasian/European Heritage
    		 3200 3179 1604 7983
        Multiple
    		 41 45 17 103
        Unknown
    		 0 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    FF/UMEC/VI
    Reporting group description
    		 The eligible participants in this arm received Fluticasone Furoate (FF)/Umeclidinium (UMEC)/Vilanterol (VI) as a fixed dose combination (FDC) as 100 microgram (µcg)/62.5µcg/25µcg once daily (QD) via a dry powder inhaler (DPI), in the morning, for duration of 52 weeks.

    Reporting group title
    FF/VI
    Reporting group description
    		 The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.

    Reporting group title
    UMEC/VI
    Reporting group description
    		 The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.

    Primary: Annual rate of on-treatment moderate/severe exacerbations comparing FF/UMEC/VI with UMEC/VI and FF/VI

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    End point title
    		 Annual rate of on-treatment moderate/severe exacerbations comparing FF/UMEC/VI with UMEC/VI and FF/VI
    End point description
    The annual rate of moderate or severe COPD, exacerbations which occurred during treatment was assessed. Moderate exacerbations were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations were defined as exacerbations that required hospitalization or resulted in death. Analysis performed using a generalized linear model assuming a negative binomial distribution. ITT population was used which comprised of all randomized participants, excluding those who were randomized in error. Only those participants with non-missing co-variates were included in the analysis.
    End point type
    Primary
    End point timeframe
    Up to Week 52
    End point values
    		 FF/UMEC/VI FF/VI UMEC/VI
    Number of subjects analysed
    4145 [1]
    4133 [2]
    2069 [3]
    Units: Exacerbations per participant per year
    least squares mean (confidence interval 95%)
        Exacerbations per participant per year
    0.91 (0.87 to 0.95)
    1.07 (1.02 to 1.12)
    1.21 (1.14 to 1.29)
    Notes
    [1] - ITT Population
    [2] - ITT Population
    [3] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted Forced expiratory volume in 1 second (FEV1) (Screening) were used.
    Comparison groups
    FF/UMEC/VI v UMEC/VI
    Number of subjects included in analysis
    6214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 < 0.001
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 0.81
    Notes
    [4] - The adjusted p-values should be compared against a reference level of 0.05 in order to infer statistical significance for either of the comparisons.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted FEV1 (Screening) were used.
    Comparison groups
    FF/VI v FF/UMEC/VI
    Number of subjects included in analysis
    8278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.001
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 0.9
    Notes
    [5] - The adjusted p-values should be compared against a reference level of 0.05 in order to infer statistical significance for either of the comparisons

    Secondary: Change from Baseline in trough FEV1, at Week 52 comparing FF/UMEC/VI with FF/VI

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    End point title
    		 Change from Baseline in trough FEV1, at Week 52 comparing FF/UMEC/VI with FF/VI [6]
    End point description
    FEV1, was defined as the amount of air a person exhales in one second. Change from Baseline, was calculated as the value of FEV1 at Week 52 minus the value at Baseline. Baseline for trough FEV1 was defined as Day 1 (Pre-dose). Only those participants with non-missing co-variates were included in the analysis. The analysis was performed using a Repeated measures model with covariates of treatment group, smoking status (Screening), geographical region, visit, Baseline, Baseline by visit and treatment group by visit interactions.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 FF/UMEC/VI FF/VI
    Number of subjects analysed
    3366 [7]
    3060 [8]
    Units: Liter
    least squares mean (standard error)
        Liter
    0.094 ± 0.0042
    -0.003 ± 0.0044
    Notes
    [7] - ITT Population
    [8] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI v FF/UMEC/VI
    Number of subjects included in analysis
    6426
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 < 0.001
    Method
    		 Mixed Models Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.097
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.085
         upper limit
    		 0.109
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0061
    Notes
    [9] - The adjusted p-value at Week 52 should be compared against a reference level of 0.05 in order to infer statistical significance for the comparison of FF/UMEC/VI versus (vs) FF/VI at Week 52.

    Secondary: Change from Baseline in St. George’s Respiratory Questionnaire for (SGRQ) Total Score at Week 52 comparing FF/UMEC/VI with FF/VI

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    End point title
    		 Change from Baseline in St. George’s Respiratory Questionnaire for (SGRQ) Total Score at Week 52 comparing FF/UMEC/VI with FF/VI [10]
    End point description
    SGRQ is a disease specific-questionnaire, designed to measure impact of respiratory disease and its treatment on a COPD participant’s Health Related Quality of Life (HRQoL). SGRQ contains 14 questions with total of 40 items grouped into three domains (Symptoms, Activity, and Impacts). The overall summary score along with scores for the individual domains of symptoms, activity and impacts were assessed. Score was calculated by summing the pre-assigned weights of answers, dividing by sum of maximum weights for items in SGRQ. Total scores ranged from 0 to 100. A decrease in score indicates improvement in HRQoL and higher score implies worse quality of life. Change from Baseline was calculated as total score at Week 52 minus value at Baseline. Baseline was defined as Day 1. Minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Only those participants with non-missing co-variates were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 FF/UMEC/VI FF/VI
    Number of subjects analysed
    3318 [11]
    3026 [12]
    Units: Scores on SGRQ scale
    least squares mean (standard error)
        Scores on SGRQ scale
    -5.5 ± 0.23
    -3.7 ± 0.24
    Notes
    [11] - ITT Population
    [12] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI v FF/UMEC/VI
    Number of subjects included in analysis
    6344
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 < 0.001
    Method
    		 Mixed Models Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 -1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [13] - The adjusted p-value at Week 52 should be compared against a reference level of 0.05 in order to infer statistical significance for the comparison of FF/UMEC/VI vs FF/VI at Week 52.

    Secondary: Time to first on-treatment moderate/severe exacerbation comparing FF/UMEC/VI with FF/VI and with UMEC/VI

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    End point title
    		 Time to first on-treatment moderate/severe exacerbation comparing FF/UMEC/VI with FF/VI and with UMEC/VI
    End point description
    This measures the number of days, to first onset of moderate or severe exacerbations. Moderate exacerbations, were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations, were defined as exacerbations that required hospitalization or resulted in death. Hazard ratio from Cox proportional hazards model with covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted FEV1 (Screening), have been reported. Only those participants with non-missing co-variates were included in analysis. The first quartile and median time to onset, are taken from the Kaplan-Meier estimates. If <25% (and <50%) of participants experienced the event within a treatment then Q1 (and median) time to onset are displayed as 99999 which is not applicable for that treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 FF/UMEC/VI FF/VI UMEC/VI
    Number of subjects analysed
    1959 [14]
    2039 [15]
    1036 [16]
    Units: Days
        First quartile time to onset
    112
    81
    73
        Median time to onset
    99999
    99999
    306
    Notes
    [14] - ITT population
    [15] - ITT population
    [16] - ITT population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/UMEC/VI v FF/VI
    Number of subjects included in analysis
    3998
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 < 0.001
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 0.91
    Notes
    [17] - The adjusted p-values should be compared against a reference level of 0.05 in order to infer statistical significance for either of the comparisons.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    UMEC/VI v FF/UMEC/VI
    Number of subjects included in analysis
    2995
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 < 0.001
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 0.91
    Notes
    [18] - The adjusted p-values should be compared against a reference level of 0.05 in order to infer statistical significance for either of the comparisons.

    Secondary: Annual rate of on-treatment moderate/severe exacerbations comparing FF/UMEC/VI with UMEC/VI in the subset of participants with a blood eosinophil count >=150 cells per microliter

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    End point title
    		 Annual rate of on-treatment moderate/severe exacerbations comparing FF/UMEC/VI with UMEC/VI in the subset of participants with a blood eosinophil count >=150 cells per microliter [19]
    End point description
    The annual rate of moderate or severe COPD exacerbations during the treatment, for participants with blood eosinophil count >=150 cells per microliter at Baseline, has been reported. Moderate exacerbations, were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations were defined as exacerbations that required hospitalization or resulted in death. Only those participants with non-missing co-variates and non-missing EOS at Baseline were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 FF/UMEC/VI UMEC/VI
    Number of subjects analysed
    2296 [20]
    1195 [21]
    Units: Exacerbations per participant per year
    least squares mean (confidence interval 95%)
        Exacerbations per participant per year
    0.95 (0.90 to 1.01)
    1.39 (1.29 to 1.51)
    Notes
    [20] - ITT population
    [21] - ITT population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/UMEC/VI v UMEC/VI
    Number of subjects included in analysis
    3491
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Negative binomial Model
    Parameter type
    		 Rate ratio
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.75

    Secondary: Time to first on-treatment moderate/severe exacerbation comparing FF/UMEC/VI with UMEC/VI in the subset of particpants with a blood eosinophil count >=150 cells per microliter at Baseline

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    End point title
    		 Time to first on-treatment moderate/severe exacerbation comparing FF/UMEC/VI with UMEC/VI in the subset of particpants with a blood eosinophil count >=150 cells per microliter at Baseline [22]
    End point description
    This measures the number of days, to the first onset of moderate or severe exacerbations for participants with blood eosinophil count >=150 cells per microliter, at Baseline has been reported. Moderate exacerbations, were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations, were defined as exacerbations that required hospitalization or resulted in death. Only those participants with non-missing co-variates and non missing EOS at Baseline were included in the analysis. First quartile and median time to onset are taken from the Kaplan-Meier estimates. If <25% (and <50%) of participants experienced the event within a treatment then Q1 (and median) time to onset are displayed as 99999, not applicable for that treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 FF/UMEC/VI UMEC/VI
    Number of subjects analysed
    2296 [23]
    1195 [24]
    Units: Days
        First quartile time to onset
    107
    55
        Median time to onset
    99999
    253
    Notes
    [23] - ITT population
    [24] - ITT population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    UMEC/VI v FF/UMEC/VI
    Number of subjects included in analysis
    3491
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 0.85

    Secondary: Annual rate of on-treatment severe exacerbations comparing FF/UMEC/VI with FF/VI and with UMEC/VI

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    End point title
    		 Annual rate of on-treatment severe exacerbations comparing FF/UMEC/VI with FF/VI and with UMEC/VI
    End point description
    The annual rate of severe COPD exacerbations during the treatment, has been reported. Severe exacerbations were defined as exacerbations that required hospitalization or resulted in death. The covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted FEV1 (Screening) were used. Only those participants with non-missing co-variates were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 FF/UMEC/VI FF/VI UMEC/VI
    Number of subjects analysed
    4145 [25]
    4133 [26]
    2069 [27]
    Units: Exacerbations per participant per year
    least squares mean (confidence interval 95%)
        Exacerbations per participant per year
    0.13 (0.12 to 0.14)
    0.15 (0.13 to 0.16)
    0.19 (0.17 to 0.22)
    Notes
    [25] - ITT population
    [26] - ITT population
    [27] - ITT population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI v FF/UMEC/VI
    Number of subjects included in analysis
    8278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.064
    Method
    		 Negative binomial model
    Parameter type
    		 Rate Ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.01
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/UMEC/VI v UMEC/VI
    Number of subjects included in analysis
    6214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 0.78

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment Serious adverse events (SAEs) and Adverse events (AEs) are reported from the first dose of randomized medication up to Week 52.
    Adverse event reporting additional description
    All AEs and SAEs in the ITT Population were reported. The number of on-treatment deaths are reported from date of first dose of study medication up to the day after the last date of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    FF/UMEC/VI 100/62.5/25
    Reporting group description
    		 The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.

    Reporting group title
    FF/VI 100/25
    Reporting group description
    		 The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.

    Reporting group title
    UMEC/VI 62.5/25
    Reporting group description
    		 The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.

    Serious adverse events
    		 FF/UMEC/VI 100/62.5/25 FF/VI 100/25 UMEC/VI 62.5/25
    Total subjects affected by serious adverse events
         subjects affected / exposed
    895 / 4151 (21.56%)
    850 / 4134 (20.56%)
    470 / 2070 (22.71%)
         number of deaths (all causes)
    68
    76
    49
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    Adenocarcinoma gastric
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign breast neoplasm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign fallopian tube neoplasm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 4151 (0.00%)
    4 / 4134 (0.10%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma stage I
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone neoplasm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    2 / 4151 (0.05%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    Breast cancer
         subjects affected / exposed
    2 / 4151 (0.05%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Colon cancer stage I
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epiglottic carcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibroma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal neoplasm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glottis carcinoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemangioma of spleen
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic angiosarcoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hepatic cancer metastatic
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hepatic neoplasm
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    4 / 4151 (0.10%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Lung adenocarcinoma stage III
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Lung carcinoma cell type unspecified stage I
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    6 / 4151 (0.14%)
    10 / 4134 (0.24%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Lung squamous cell carcinoma stage II
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm of ampulla of Vater
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm of unknown primary site
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Metastases to liver
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Monoclonal gammopathy
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine tumour of the lung
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    2 / 4151 (0.05%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Oral neoplasm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    3 / 4151 (0.07%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Papilloma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    4 / 4151 (0.10%)
    4 / 4134 (0.10%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyogenic granuloma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sarcoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Small cell lung cancer metastatic
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Small intestine carcinoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue sarcoma
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    3 / 4151 (0.07%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Squamous cell carcinoma of the cervix
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Throat cancer
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethral cancer
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vulval cancer
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Acute aortic syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aneurysm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm rupture
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolism arterial
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral artery aneurysm
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemodynamic instability
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    3 / 4151 (0.07%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    3 / 4151 (0.07%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Varicose ulceration
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Surgical and medical procedures
    Hernia repair
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    5 / 4151 (0.12%)
    3 / 4134 (0.07%)
    7 / 2070 (0.34%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Condition aggravated
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    3 / 4151 (0.07%)
    5 / 4134 (0.12%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 3
    0 / 5
    0 / 2
    General physical health deterioration
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Implant site fibrosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical device site haemorrhage
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    8 / 4151 (0.19%)
    10 / 4134 (0.24%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 10
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stent-graft endoleak
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    Sudden death
         subjects affected / exposed
    3 / 4151 (0.07%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 3
    0 / 2
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Allergy to arthropod sting
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Anaphylactic shock
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Drug hypersensitivity
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 4151 (0.05%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystocele
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    23 / 4151 (0.55%)
    17 / 4134 (0.41%)
    16 / 2070 (0.77%)
         occurrences causally related to treatment / all
    2 / 27
    1 / 17
    0 / 20
         deaths causally related to treatment / all
    1 / 4
    0 / 3
    0 / 4
    Asthma-chronic obstructive pulmonary disease overlap syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Choking
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    443 / 4151 (10.67%)
    450 / 4134 (10.89%)
    269 / 2070 (13.00%)
         occurrences causally related to treatment / all
    21 / 554
    27 / 569
    16 / 337
         deaths causally related to treatment / all
    1 / 13
    1 / 22
    1 / 11
    Chronic respiratory failure
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 4151 (0.07%)
    4 / 4134 (0.10%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 4151 (0.02%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    3 / 4151 (0.07%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasal polyps
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal oedema
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pickwickian syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 4151 (0.05%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    3 / 4151 (0.07%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    8 / 4151 (0.19%)
    11 / 4134 (0.27%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    2 / 13
    0 / 12
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    5 / 4151 (0.12%)
    5 / 4134 (0.12%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    7 / 4151 (0.17%)
    7 / 4134 (0.17%)
    6 / 2070 (0.29%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
    1 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
    Pulmonary granuloma
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hilum mass
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Respiratory acidosis
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Respiratory distress
         subjects affected / exposed
    2 / 4151 (0.05%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    22 / 4151 (0.53%)
    21 / 4134 (0.51%)
    7 / 2070 (0.34%)
         occurrences causally related to treatment / all
    1 / 23
    3 / 21
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    1 / 4
    0 / 1
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    2 / 4151 (0.05%)
    4 / 4134 (0.10%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Psychotic disorder due to a general medical condition
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Substance-induced psychotic disorder
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Biopsy prostate
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibrin D dimer increased
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    3 / 4151 (0.07%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Occult blood positive
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcus test positive
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Alcohol poisoning
         subjects affected / exposed
    4 / 4151 (0.10%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chemical peritonitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Chest injury
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Conjunctival laceration
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 4151 (0.05%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foreign body aspiration
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Gastrointestinal disorder postoperative
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Heat illness
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    4 / 4151 (0.10%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    4 / 4151 (0.10%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaw fracture
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    3 / 4151 (0.07%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Muscle rupture
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural stroke
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    9 / 4151 (0.22%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin injury
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stress fracture
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound evisceration
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Developmental hip dysplasia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydrocele
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial bridging
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Odontogenic cyst
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    13 / 4151 (0.31%)
    8 / 4134 (0.19%)
    6 / 2070 (0.29%)
         occurrences causally related to treatment / all
    1 / 14
    1 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    2 / 4151 (0.05%)
    3 / 4134 (0.07%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    7 / 4151 (0.17%)
    6 / 4134 (0.15%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 6
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    21 / 4151 (0.51%)
    13 / 4134 (0.31%)
    6 / 2070 (0.29%)
         occurrences causally related to treatment / all
    4 / 24
    3 / 13
    1 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    Atrial flutter
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular dissociation
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    3 / 4151 (0.07%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    4 / 4151 (0.10%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
    Cardiac disorder
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    12 / 4151 (0.29%)
    7 / 4134 (0.17%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    2 / 4151 (0.05%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    21 / 4151 (0.51%)
    12 / 4134 (0.29%)
    7 / 2070 (0.34%)
         occurrences causally related to treatment / all
    0 / 28
    1 / 12
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Cardiac valve disease
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    4 / 4151 (0.10%)
    4 / 4134 (0.10%)
    5 / 2070 (0.24%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 4
    1 / 4
    0 / 5
    Cardiogenic shock
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cor pulmonale chronic
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    4 / 4151 (0.10%)
    2 / 4134 (0.05%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Coronary artery occlusion
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    10 / 4151 (0.24%)
    6 / 4134 (0.15%)
    7 / 2070 (0.34%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Myocardial ischaemia
         subjects affected / exposed
    5 / 4151 (0.12%)
    1 / 4134 (0.02%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prinzmetal angina
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    2 / 4151 (0.05%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain stem ischaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain stem stroke
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    4 / 4151 (0.10%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral amyloid angiopathy
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    3 / 4151 (0.07%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    7 / 4151 (0.17%)
    6 / 4134 (0.15%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cerebrovascular insufficiency
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    4 / 4151 (0.10%)
    5 / 4134 (0.12%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental impairment
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myoclonus
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral nerve paresis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radicular syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    3 / 4151 (0.07%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Simple partial seizures
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    6 / 4151 (0.14%)
    5 / 4134 (0.12%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Tension headache
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    8 / 4151 (0.19%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    4 / 4134 (0.10%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic disorder
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Meniere's disease
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Amaurosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    3 / 4151 (0.07%)
    5 / 4134 (0.12%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cataract nuclear
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal compartment syndrome
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal discomfort
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    3 / 4151 (0.07%)
    4 / 4134 (0.10%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 4151 (0.05%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erosive duodenitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    4 / 4151 (0.10%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 4151 (0.02%)
    4 / 4134 (0.10%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    6 / 4151 (0.14%)
    4 / 4134 (0.10%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Intestinal perforation
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    2 / 4151 (0.05%)
    2 / 4134 (0.05%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic cyst
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic failure
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    4 / 4151 (0.10%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal fibrosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 4151 (0.05%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    3 / 4151 (0.07%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    5 / 2070 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder perforation
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder polyp
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dermatitis allergic
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkeratosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuropathic ulcer
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peau d'orange
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pustular psoriasis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    6 / 4151 (0.14%)
    9 / 4134 (0.22%)
    6 / 2070 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 9
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Bladder disorder
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder stenosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus bladder
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    End stage renal disease
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 4151 (0.05%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Renal aneurysm
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cyst haemorrhage
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    3 / 4151 (0.07%)
    3 / 4134 (0.07%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vesicocutaneous fistula
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal mass
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 4151 (0.10%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone infarction
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dupuytren's contracture
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoroacetabular impingement
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 4151 (0.02%)
    3 / 4134 (0.07%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 4151 (0.05%)
    4 / 4134 (0.10%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    9 / 4151 (0.22%)
    5 / 4134 (0.12%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal deformity
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal ligament ossification
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spondylitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendiceal abscess
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspergillus infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    10 / 4151 (0.24%)
    10 / 4134 (0.24%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 11
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carbuncle
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    6 / 4151 (0.14%)
    1 / 4134 (0.02%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis staphylococcal
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridial infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic abscess
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Corona virus infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    3 / 4151 (0.07%)
    3 / 4134 (0.07%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis bacterial
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteritis infectious
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fungal oesophagitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 4151 (0.02%)
    5 / 4134 (0.12%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Haemophilus infection
         subjects affected / exposed
    3 / 4151 (0.07%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Helicobacter gastritis
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Helicobacter infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected varicose vein
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    8 / 4151 (0.19%)
    19 / 4134 (0.46%)
    7 / 2070 (0.34%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 20
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    7 / 4151 (0.17%)
    6 / 4134 (0.15%)
    5 / 2070 (0.24%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Kidney infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    7 / 4151 (0.17%)
    4 / 4134 (0.10%)
    4 / 2070 (0.19%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mycobacterial infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mycoplasma infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nosocomial infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parotitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    184 / 4151 (4.43%)
    152 / 4134 (3.68%)
    54 / 2070 (2.61%)
         occurrences causally related to treatment / all
    36 / 198
    20 / 165
    12 / 55
         deaths causally related to treatment / all
    0 / 10
    0 / 5
    0 / 3
    Pneumonia bacterial
         subjects affected / exposed
    2 / 4151 (0.05%)
    9 / 4134 (0.22%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    3 / 9
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pyelonephritis acute
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection bacterial
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    3 / 4134 (0.07%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    9 / 4151 (0.22%)
    8 / 4134 (0.19%)
    6 / 2070 (0.29%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Sepsis syndrome
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    4 / 4151 (0.10%)
    2 / 4134 (0.05%)
    3 / 2070 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Sinusitis
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Streptococcal infection
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subacute endocarditis
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdiaphragmatic abscess
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Superinfection
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Tonsillitis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    4 / 4151 (0.10%)
    7 / 4134 (0.17%)
    4 / 2070 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Urosepsis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acetonaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    4 / 4151 (0.10%)
    5 / 4134 (0.12%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    3 / 4151 (0.07%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 4151 (0.02%)
    1 / 4134 (0.02%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    2 / 4151 (0.05%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    0 / 4151 (0.00%)
    0 / 4134 (0.00%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    3 / 4151 (0.07%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    7 / 4151 (0.17%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    5 / 4151 (0.12%)
    1 / 4134 (0.02%)
    2 / 2070 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Hypophagia
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    2 / 4151 (0.05%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    1 / 4151 (0.02%)
    0 / 4134 (0.00%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 4151 (0.00%)
    2 / 4134 (0.05%)
    1 / 2070 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitamin B12 deficiency
         subjects affected / exposed
    0 / 4151 (0.00%)
    1 / 4134 (0.02%)
    0 / 2070 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 FF/UMEC/VI 100/62.5/25 FF/VI 100/25 UMEC/VI 62.5/25
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1389 / 4151 (33.46%)
    1278 / 4134 (30.91%)
    596 / 2070 (28.79%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    233 / 4151 (5.61%)
    197 / 4134 (4.77%)
    101 / 2070 (4.88%)
         occurrences all number
    385
    332
    139
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    145 / 4151 (3.49%)
    117 / 4134 (2.83%)
    58 / 2070 (2.80%)
         occurrences all number
    168
    128
    75
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    146 / 4151 (3.52%)
    139 / 4134 (3.36%)
    83 / 2070 (4.01%)
         occurrences all number
    180
    164
    101
    Infections and infestations
    Viral upper respiratory tract infection
         subjects affected / exposed
    520 / 4151 (12.53%)
    479 / 4134 (11.59%)
    222 / 2070 (10.72%)
         occurrences all number
    712
    658
    316
    Upper respiratory tract infection
         subjects affected / exposed
    297 / 4151 (7.15%)
    283 / 4134 (6.85%)
    117 / 2070 (5.65%)
         occurrences all number
    401
    383
    162
    Oral candidiasis
         subjects affected / exposed
    161 / 4151 (3.88%)
    146 / 4134 (3.53%)
    41 / 2070 (1.98%)
         occurrences all number
    203
    176
    50
    Bronchitis
         subjects affected / exposed
    142 / 4151 (3.42%)
    120 / 4134 (2.90%)
    70 / 2070 (3.38%)
         occurrences all number
    165
    152
    83
    Pneumonia
         subjects affected / exposed
    121 / 4151 (2.91%)
    127 / 4134 (3.07%)
    41 / 2070 (1.98%)
         occurrences all number
    131
    135
    43

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Mar 2014
    Clarified approval status of products in the protocol, added wording concerning hematology collection, and corrected minor errors in the Time and Events Table
    10 Apr 2014
    Added post-bronchodilator FEV1 to each visit and included this as an other efficacy endpoint. A mortality endpoint was also added as an other efficacy endpoint. Other changes included changing the predicted FEV1 reference values from NHANES III to the European Respiratory Society Global Lung Function Initiative and to correct minor errors in CAT, contraceptive methods, and ECG wording.
    05 Dec 2014
    Clarified that SAEs in China would be recorded from the time the consent form was signed until the 7-day safety follow-up visit/telephone contact had been completed, or until Visit 7 (telephone contact) for participant who discontinued study treatment but continued in the study
    12 May 2015
    Clarified that none of the study sites in China would participate in genetic research in this study and addition of a China-specific sub-study to collect the unit-cost data for healthcare utilization among participants recruited in China.
    30 Jun 2016
    Simplified the statistical hierarchy for the analysis of secondary endpoints. In addition, there were minor changes to the definitions of the analysis populations, changes in model terms that were included in the primary efficacy endpoint analysis, and clarification on the primary endpoint sensitivity analysis. For the safety analysis, there were minor changes to clarify the analyses of Pneumonia AEs and Major Adverse Cardiac Events (MACE)

    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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