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    Clinical Trial Results:
    Phase 3 Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Evaluation of the Efficacy, Safety, and Tolerability of Bococizumab (PF-04950615), in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects

    Summary
    EudraCT number
    		 2013-002646-36
    Trial protocol
    		 GB   NL   FI   DE   HU   CZ   SE   SK   ES   IT   BE   DK   PL   IE  
    Global end of trial date
    22 Mar 2017

    Results information
    Results version number
    		 v1
    This version publication date
    10 Nov 2017
    First version publication date
    10 Nov 2017
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    B1481022
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01975376
    WHO universal trial number (UTN)
    		 U1111-1151-0594
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Sep 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Mar 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To demonstrate the superior efficacy of bococizumab compared with placebo in reducing the risk of major CV events, a composite endpoint which included adjudicated and confirmed CV death, non-fatal MI, non-fatal stroke, and hospitalization for unstable angina with urgent revascularization, in subjects at high or very high risk of major CV events who were on background lipid-lowering treatment and had an LDL-C >=70 mg/dL (1.81 mmol/L) or non-HDL-C >=100 mg/dL (2.59 mmol/L).
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines and all local regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Oct 2013
    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: 776
    Country: Number of subjects enrolled
    Australia: 165
    Country: Number of subjects enrolled
    Belgium: 166
    Country: Number of subjects enrolled
    Brazil: 1553
    Country: Number of subjects enrolled
    Canada: 482
    Country: Number of subjects enrolled
    Chile: 104
    Country: Number of subjects enrolled
    China: 338
    Country: Number of subjects enrolled
    Colombia: 228
    Country: Number of subjects enrolled
    Czech Republic: 310
    Country: Number of subjects enrolled
    Denmark: 328
    Country: Number of subjects enrolled
    Finland: 281
    Country: Number of subjects enrolled
    France: 190
    Country: Number of subjects enrolled
    Germany: 1029
    Country: Number of subjects enrolled
    Hungary: 413
    Country: Number of subjects enrolled
    Ireland: 8
    Country: Number of subjects enrolled
    Israel: 278
    Country: Number of subjects enrolled
    Italy: 71
    Country: Number of subjects enrolled
    Korea, Republic of: 104
    Country: Number of subjects enrolled
    Mexico: 367
    Country: Number of subjects enrolled
    Netherlands: 1016
    Country: Number of subjects enrolled
    New Zealand: 113
    Country: Number of subjects enrolled
    Poland: 1486
    Country: Number of subjects enrolled
    Puerto Rico: 28
    Country: Number of subjects enrolled
    Romania: 186
    Country: Number of subjects enrolled
    Russian Federation: 415
    Country: Number of subjects enrolled
    Slovakia: 439
    Country: Number of subjects enrolled
    South Africa: 453
    Country: Number of subjects enrolled
    Spain: 482
    Country: Number of subjects enrolled
    Sweden: 272
    Country: Number of subjects enrolled
    Switzerland: 64
    Country: Number of subjects enrolled
    Taiwan: 49
    Country: Number of subjects enrolled
    Thailand: 41
    Country: Number of subjects enrolled
    Turkey: 47
    Country: Number of subjects enrolled
    United Kingdom: 654
    Country: Number of subjects enrolled
    United States: 3848
    Worldwide total number of subjects
    16784
    EEA total number of subjects
    7331
    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)
    8994
    From 65 to 84 years
    7715
    85 years and over
    75

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents.

    Pre-assignment
    Screening details
    		 Study was conducted at multiple sites from 29 October 2013 to 22 March 2017. However, subjects were screened from 29 October 2013 through 01 November 2016.

    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, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matched to PF-04950615 subcutaneous injection once in every 2 Weeks over a period of 3.3 years.

    Arm title
    		 Bococizumab (PF-04950615)
    Arm description
    		 Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bococizumab
    Investigational medicinal product code
    PF-04950615
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    150 milligrams, subcutaneous injection once in every 2 Weeks over a period of 3.3 years.

    Number of subjects in period 1
    		Placebo Bococizumab (PF-04950615)
    Started
    8390
    8394
    Received treatment
    8374
    8386
    Completed
    8169
    8179
    Not completed
    221
    215
         Adverse event, serious fatal
    65
    72
         Adverse event, non-fatal
    6
    5
         Unspecified
    8
    8
         Lost to follow-up
    70
    66
         Withdrew consent
    72
    64

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.

    Reporting group title
    Bococizumab (PF-04950615)
    Reporting group description
    		 Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.

    Reporting group values
    		 Placebo Bococizumab (PF-04950615) Total
    Number of subjects
    		 8390 8394 16784
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 4496 4498 8994
        From 65-84 years
    		 3853 3862 7715
        85 years and over
    		 41 34 75
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 63.3 ( 9.2 ) 63.3 ( 9.1 ) -
    Gender, Male/Female
    Units: Subjects
        Female
    		 2223 2207 4430
        Male
    		 6167 6187 12354

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.

    Reporting group title
    Bococizumab (PF-04950615)
    Reporting group description
    		 Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.

    Primary: Event Rate Per 100 Subject-Years For First Occurrence of Major Cardiovascular (CV) Event

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    End point title
    		 Event Rate Per 100 Subject-Years For First Occurrence of Major Cardiovascular (CV) Event
    End point description
    Event rate per 100 Subject-years for first occurrence of major CV event (adjudicated by Adjudication Committee) was reported. Major CV event was defined as any of the following: CV death (defined as sudden cardiac death, fatal myocardial infarction [MI], death due to heart failure, death due to stroke [fatal ischemic stroke or fatal stroke of undetermined etiology], or death due to other cardiovascular causes) non-fatal MI, non-fatal stroke, and hospitalization for unstable angina needing urgent revascularization. Event rate was calculated as the number of events per 100 Subject-years at risk. Full analysis set (FAS): all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Primary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.3 years).
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events Per 100 Subject-Years
        number (confidence interval 95%)
    3.02 (2.59 to 3.51)
    3.01 (2.58 to 3.50)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95 percent (%) Confidence Interval (CI) were from a Cox proportional hazards model stratified by geographic region and Low density lipoprotein cholesterol (LDL-C) at pre-screening (less than [<] 100 milligrams per deciliters [mg/dL], greater than and equal to [>=] 100 mg/dL) with treatment as a co-variate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.930905
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.22

    Secondary: Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infraction, or Non-Fatal Stroke

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infraction, or Non-Fatal Stroke
    End point description
    Cardiovascular death is defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke [fatal ischemic stroke or fatal stroke of undetermined etiology], or death due to other cardiovascular causes). Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of the cardiovascular death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    2.49 (2.10 to 2.93)
    2.59 (2.19 to 3.04)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.784265
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.3

    Secondary: Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infraction, Non-Fatal Stroke, or Hospitalization for Unstable Angina Needing Urgent Revascularization

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infraction, Non-Fatal Stroke, or Hospitalization for Unstable Angina Needing Urgent Revascularization
    End point description
    Event rate per 100 Subject-years for first occurrence of composite endpoint of all-cause death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    3.51 (3.04 to 4.03)
    3.48 (3.02 to 4.00)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.892441
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.2

    Secondary: Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infarction, or Non-Fatal Stroke

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infarction, or Non-Fatal Stroke
    End point description
    Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI, or non-fatal stroke (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of the all-cause death, non-fatal MI, or non-fatal stroke (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    2.98 (2.55 to 3.46)
    3.06 (2.62 to 3.54)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.845797
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.26

    Secondary: Event rate per 100 Subject-years For First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization
    End point description
    Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.57 (0.39 to 0.80)
    0.47 (0.31 to 0.68)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.431903
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 1.36

    Secondary: Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke and Hospitalization for Unstable Angina

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke and Hospitalization for Unstable Angina
    End point description
    Event rate per 100 participant-years for first occurrence of composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. Cardiovascular death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other cardiovascular causes. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of cardiovascular death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    3.22 (2.77 to 3.72)
    3.19 (2.74 to 3.69)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.883797
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.21

    Secondary: Event rate per 100 Subject-years For Cardiovascular Death

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    End point title
    		 Event rate per 100 Subject-years For Cardiovascular Death
    End point description
    Event rate per 100 participant-years for cardiovascular death (adjudicated by Adjudication Committee) was reported. Cardiovascular death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other cardiovascular causes. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of adjudicated and confirmed occurrence of cardiovascular death (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.52 (0.35 to 0.74)
    0.64 (0.45 to 0.88)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.45569
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.95

    Secondary: Event rate per 100 Subject-years For First Occurrence of any Myocardial Infarction (Fatal or Non-Fatal)

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of any Myocardial Infarction (Fatal or Non-Fatal)
    End point description
    Event rate per 100 participant-years for first occurrence of any MI (Fatal or Non-Fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of any MI (fatal or non-fatal) (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    1.56 (1.26 to 1.92)
    1.74 (1.41 to 2.11)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.469496
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.48

    Secondary: Event rate per 100 Subject-years For Fatal Myocardial Infarction

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    End point title
    		 Event rate per 100 Subject-years For Fatal Myocardial Infarction
    End point description
    Event rate per 100 participant-years for fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of adjudicated and confirmed occurrence of fatal MI (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.03 (0.00 to 0.12)
    0.05 (0.01 to 0.15)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.633022
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 9.23

    Secondary: Event rate per 100 Subject-years For First Occurrence of Non-Fatal Myocardial Infarction

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Non-Fatal Myocardial Infarction
    End point description
    Event rate per 100 participant-years for first occurrence of non-fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of non-fatal MI (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    1.53 (1.23 to 1.88)
    1.70 (1.38 to 2.07)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.46765
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.48

    Secondary: Event rate per 100 Subject-years For First Occurrence of Any Stroke (Fatal or Non-Fatal)

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Any Stroke (Fatal or Non-Fatal)
    End point description
    Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.71 (0.51 to 0.96)
    0.38 (0.24 to 0.57)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.015462
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 0.89

    Secondary: Event rate per 100 Subject-years For First Occurrence of Any Stroke (Fatal or Non-Fatal), of Any Etiology

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Any Stroke (Fatal or Non-Fatal), of Any Etiology
    End point description
    Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal), of any etiology (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal), of any etiology (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.79 (0.58 to 1.06)
    0.43 (0.28 to 0.64)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011863
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 0.88

    Secondary: Event rate per 100 Subject-years For Fatal Stroke

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    End point title
    		 Event rate per 100 Subject-years For Fatal Stroke
    End point description
    Event rate per 100 participant-years for fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.10 (0.04 to 0.22)
    0.05 (0.01 to 0.15)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.316066
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.12
         upper limit
    		 2

    Secondary: Event rate per 100 Subject-years For First Occurrence of Non-Fatal Stroke

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Non-Fatal Stroke
    End point description
    Event rate per 100 participant-years for first occurrence of non-fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of non-fatal stroke (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.62 (0.44 to 0.86)
    0.33 (0.20 to 0.51)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.020328
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 0.91

    Secondary: Event rate per 100 Subject-years For First Occurrence of Hospitalization for Unstable Angina

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Hospitalization for Unstable Angina
    End point description
    Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.78 (0.57 to 1.04)
    0.64 (0.45 to 0.88)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.367069
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.27

    Secondary: Event rate per 100 Subject-years For First Occurrence of Hospitalization for Congestive Heart Failure (CHF)

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Hospitalization for Congestive Heart Failure (CHF)
    End point description
    Event rate per 100 participant-years for first occurrence of hospitalization for CHF (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for congestive heart failure (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.81 (0.60 to 1.08)
    0.69 (0.49 to 0.94)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.443081
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 1.29

    Secondary: Event rate per 100 Subject-years For First Occurrence of Coronary Revascularization

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Coronary Revascularization
    End point description
    Event rate per 100 participant-years for first occurrence of coronary revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of coronary revascularization (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    2.74 (2.33 to 3.20)
    2.45 (2.06 to 2.89)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.343817
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.12

    Secondary: Event rate per 100 Subject-years For First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)
    End point description
    Event rate per 100 participant-years for first occurrence of CABG (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of CABG (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    0.40 (0.25 to 0.60)
    0.41 (0.26 to 0.61)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.889065
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.85

    Secondary: Event rate per 100 Subject-years For First Occurrence of Percutaneous Coronary Intervention (PCI)

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Percutaneous Coronary Intervention (PCI)
    End point description
    Event rate per 100 participant-years for first occurrence of PCI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of PCI (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    2.37 (1.99 to 2.80)
    2.08 (1.73 to 2.49)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.308388
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.13

    Secondary: Event rate per 100 Subject-years For First Occurrence of Any Arterial Revascularizations

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    End point title
    		 Event rate per 100 Subject-years For First Occurrence of Any Arterial Revascularizations
    End point description
    Event rate per 100 participant-years for first occurrence of any arterial revascularizations (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of first adjudicated and confirmed occurrence of any arterial revascularizations (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    1.26 (0.99 to 1.59)
    1.28 (1.00 to 1.61)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.874835
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.42

    Secondary: Event rate per 100 Subject-years For All-Cause Death

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    End point title
    		 Event rate per 100 Subject-years For All-Cause Death
    End point description
    Event rate per 100 participant-years for all-cause death (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 subject-years at risk. FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified.
    End point type
    Secondary
    End point timeframe
    From baseline until the date of adjudicated and confirmed occurrence of all-cause death (maximum duration: up to 3.3 years)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Events per 100 Subject-years
        number (confidence interval 95%)
    1.00 (0.76 to 1.29)
    1.13 (0.88 to 1.44)
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.526269
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.6

    Secondary: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14

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    End point title
    		 Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14
    End point description
    FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "Number of subjects analyzed "(N) signifies those subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 14
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    6448
    6439
    Units: Percent change
        least squares mean (standard error)
    3.40 ( 0.31 )
    -57.17 ( 0.31 )
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Lease Square (LS)- mean differences, associated 95% CI, and p-values were from a mixed model repeated measures (MMRM) model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    12887
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-mean difference
    Point estimate
    -60.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -61.43
         upper limit
    		 -59.71

    Secondary: Nominal Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14

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    End point title
    		 Nominal Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14
    End point description
    FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "N" signifies number of subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 14
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    6448
    6439
    Units: mg/dL
        least squares mean (standard error)
    2.33 ( 0.28 )
    -52.37 ( 0.28 )
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS- mean differences and associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    12887
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-mean difference
    Point estimate
    -54.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -55.48
         upper limit
    		 -53.92

    Secondary: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Last Post-Baseline Measurement

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    End point title
    		 Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Last Post-Baseline Measurement
    End point description
    FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "N" signifies number of subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, last post-baseline measurement (any time up to Week 140)
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8240
    8254
    Units: Percent Change
        least squares mean (standard error)
    5.05 ( 0.35 )
    -41.67 ( 0.35 )
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS- mean difference and associated 95% CI, and p-value were from an analysis of covariance (ANCOVA) model with fixed effects for treatment group, baseline value, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16494
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS-mean difference
    Point estimate
    -46.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -47.68
         upper limit
    		 -45.76

    Secondary: Percent Change From Baseline in Lipid Levels at Week 14

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    End point title
    		 Percent Change From Baseline in Lipid Levels at Week 14
    End point description
    Lipids included non-high density lipoprotein cholesterol (non-HDL-C), total cholesterol, very low density lipoprotein cholesterol (VLDL-C), remnant lipoprotein cholesterol (RLP-C), apolipoprotein B (Apo B), HDL-C and apolipoprotein A-I (Apo A-I). FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "n" signifies number of subjects who were evaluable at the specified categories for each arm respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 14
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Percent Change
    least squares mean (standard error)
        Non-HDL-C (n=6427,6412)
    3.21 ( 0.28 )
    -51.66 ( 0.28 )
        Total cholesterol (n=6441, 6431)
    2.38 ( 0.20 )
    -34.13 ( 0.20 )
        VLDL-C (n=6443, 6433)
    6.52 ( 0.45 )
    -13.65 ( 0.45 )
        RLP-C (n=6418, 6400)
    9.23 ( 0.79 )
    -21.02 ( 0.79 )
        Apo B (n= 5887, 5894)
    2.80 ( 0.31 )
    -55.76 ( 0.31 )
        HDL-C (n= 6431, 6412)
    1.19 ( 0.16 )
    7.33 ( 0.16 )
        Apo A-I (n= 5890, 5896)
    1.21 ( 0.18 )
    4.74 ( 0.18 )
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Non-HDL-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-mean difference
    Point estimate
    -54.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -55.66
         upper limit
    		 -54.09
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Total cholesterol: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-mean difference
    Point estimate
    -36.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -37.07
         upper limit
    		 -35.95
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    VLDL-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-mean difference
    Point estimate
    -20.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.42
         upper limit
    		 -18.93
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    RLP-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-Mean Difference
    Point estimate
    -30.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.44
         upper limit
    		 -28.07
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Apo B: LS -mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-Mean Difference
    Point estimate
    -58.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -59.42
         upper limit
    		 -57.69
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    HDL-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-Mean Difference
    Point estimate
    6.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.69
         upper limit
    		 6.59
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Apo A-I: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit,treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-Mean Difference
    Point estimate
    3.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.02
         upper limit
    		 4.03

    Secondary: Percent Change From Baseline in Log-Transformed Lipoprotein (a) (Lp[a]) and Triglycerides at Week 14

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    End point title
    		 Percent Change From Baseline in Log-Transformed Lipoprotein (a) (Lp[a]) and Triglycerides at Week 14
    End point description
    FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "n" signifies number of subjects who were evaluable at the specified categories for each arm respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 14
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    8390
    8394
    Units: Percent Change
    arithmetic mean (standard deviation)
        Lp(a) (n=5914, 5916)
    -1.3 ( 28.81 )
    -33.9 ( 29.62 )
        Triglycerides (n= 6443, 6433)
    0.6 ( 32.84 )
    -18.9 ( 28.44 )
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Lp (a): LS- mean differences and associated 95% CI, and p-values were from an MMRM model on the difference of log-transformed observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement (M
    Parameter type
    		 LS-mean difference
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.68
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Triglycerides: LS- mean differences and associated 95% CI, and p-values were from an MMRM model through Week 70 on the difference of log-transformed observations with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    16784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-mean difference
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 0.81

    Secondary: Percent Change From Baseline in Log-Transformed High Sensitivity C- Reactive Protein (hs-CRP) at Week 14

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    End point title
    		 Percent Change From Baseline in Log-Transformed High Sensitivity C- Reactive Protein (hs-CRP) at Week 14
    End point description
    FAS: all subjects who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/ B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "N" signifies number of subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 14
    End point values
    		 Placebo Bococizumab (PF-04950615)
    Number of subjects analysed
    5931
    5930
    Units: Percent change
        arithmetic mean (standard deviation)
    -6.5 ( 88.28 )
    -1.1 ( 91.91 )
    Statistical analysis title
    		 Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS- mean differences and associated 95% CI, and p-values were from an MMRM model on the difference of log-transformed observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
    Comparison groups
    Placebo v Bococizumab (PF-04950615)
    Number of subjects included in analysis
    11861
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed Effect Model Repeat Measurement
    Parameter type
    		 LS-mean difference
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 1.1

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 3.3 years
    Adverse event reporting additional description
    Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Bococizumab (PF-04950615)
    Reporting group description
    		 Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose.

    Serious adverse events
    		 Bococizumab (PF-04950615) Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1060 / 8386 (12.64%)
    986 / 8374 (11.77%)
         number of deaths (all causes)
    43
    40
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal squamous cell carcinoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign gastrointestinal neoplasm
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct cancer
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bladder cancer
         subjects affected / exposed
    4 / 8386 (0.05%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder papilloma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma stage I
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone cancer
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer recurrent
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholesteatoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic myelomonocytic leukaemia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer stage III
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric adenoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal stromal tumour
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal cancer
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intestinal adenocarcinoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraocular melanoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large cell lung cancer
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip and/or oral cavity cancer stage 0
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liposarcoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma metastatic
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung neoplasm
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    5 / 8386 (0.06%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung squamous cell carcinoma stage III
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    3 / 8386 (0.04%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Maxillofacial sinus neoplasm
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesothelioma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to bone
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to spine
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic malignant melanoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal neoplasm
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian adenoma
    Additional description: This is gender specific event.
         subjects affected / exposed [1]
    1 / 2206 (0.05%)
    0 / 2216 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Prostate cancer
    Additional description: This is gender specific event.
         subjects affected / exposed [2]
    13 / 6180 (0.21%)
    12 / 6158 (0.19%)
         occurrences causally related to treatment / all
    0 / 13
    1 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer metastatic
    Additional description: This is gender specific event.
         subjects affected / exposed [3]
    1 / 6180 (0.02%)
    1 / 6158 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic adenoma
    Additional description: This is gender specific event.
         subjects affected / exposed [4]
    0 / 6180 (0.00%)
    1 / 6158 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 8386 (0.01%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Renal cancer recurrent
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Soft tissue neoplasm
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the cervix
    Additional description: This is gender specific event.
         subjects affected / exposed [5]
    0 / 2206 (0.00%)
    1 / 2216 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
    Additional description: This is gender specific event.
         subjects affected / exposed [6]
    1 / 2206 (0.05%)
    2 / 2216 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aneurysm
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    5 / 8386 (0.06%)
    9 / 8374 (0.11%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteritis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachiocephalic vein stenosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dry gangrene
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism arterial
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral artery aneurysm
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Granulomatosis with polyangiitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    8 / 8386 (0.10%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    2 / 8386 (0.02%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    8 / 8386 (0.10%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infarction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    1 / 8386 (0.01%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoedema
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    11 / 8386 (0.13%)
    7 / 8374 (0.08%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery dissection
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    12 / 8386 (0.14%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    9 / 8386 (0.11%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    8 / 8386 (0.10%)
    7 / 8374 (0.08%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post thrombotic syndrome
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian artery occlusion
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian artery stenosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hospitalisation
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
    Additional description: This is gender specific event.
         subjects affected / exposed [7]
    1 / 2206 (0.05%)
    0 / 2216 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 8386 (0.00%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac death
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    15 / 8386 (0.18%)
    16 / 8374 (0.19%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    15 / 8386 (0.18%)
    10 / 8374 (0.12%)
         occurrences causally related to treatment / all
    1 / 15
    3 / 10
         deaths causally related to treatment / all
    3 / 4
    1 / 1
    Electrocution
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperplasia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ill-defined disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site hypersensitivity
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site reaction
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    3 / 8386 (0.04%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Mucosal inflammation
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    45 / 8386 (0.54%)
    47 / 8374 (0.56%)
         occurrences causally related to treatment / all
    1 / 47
    1 / 50
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic mass
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    5 / 8386 (0.06%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Sudden cardiac death
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent restenosis
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent thrombosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Pregnancy of partner
    Additional description: This is gender specific event.
         subjects affected / exposed [8]
    1 / 6180 (0.02%)
    1 / 6158 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
    Additional description: This is gender specific event.
         subjects affected / exposed [9]
    1 / 6180 (0.02%)
    5 / 6158 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystocele
    Additional description: This is gender specific event.
         subjects affected / exposed [10]
    0 / 2206 (0.00%)
    1 / 2216 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fallopian tube obstruction
    Additional description: This is gender specific event.
         subjects affected / exposed [11]
    1 / 2206 (0.05%)
    0 / 2216 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genital prolapse
    Additional description: This is gender specific event.
         subjects affected / exposed [12]
    1 / 2206 (0.05%)
    0 / 2216 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menorrhagia
    Additional description: This is gender specific event.
         subjects affected / exposed [13]
    0 / 2206 (0.00%)
    1 / 2216 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
    Additional description: This is gender specific event.
         subjects affected / exposed [14]
    0 / 2206 (0.00%)
    1 / 2216 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic dysplasia
    Additional description: This is gender specific event.
         subjects affected / exposed [15]
    0 / 6180 (0.00%)
    1 / 6158 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic obstruction
    Additional description: This is gender specific event.
         subjects affected / exposed [16]
    1 / 6180 (0.02%)
    0 / 6158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
    Additional description: This is gender specific event.
         subjects affected / exposed [17]
    1 / 6180 (0.02%)
    1 / 6158 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatomegaly
    Additional description: This is gender specific event.
         subjects affected / exposed [18]
    0 / 6180 (0.00%)
    1 / 6158 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectocele
    Additional description: This is gender specific event.
         subjects affected / exposed [19]
    0 / 2206 (0.00%)
    1 / 2216 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine polyp
    Additional description: This is gender specific event.
         subjects affected / exposed [20]
    1 / 2206 (0.05%)
    0 / 2216 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
    Additional description: This is gender specific event.
         subjects affected / exposed [21]
    0 / 2206 (0.00%)
    1 / 2216 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
    Additional description: This is gender specific event.
         subjects affected / exposed [22]
    0 / 2206 (0.00%)
    1 / 2216 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
    Additional description: This is gender specific event.
         subjects affected / exposed [23]
    1 / 2206 (0.05%)
    0 / 2216 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal ulceration
    Additional description: This is gender specific event.
         subjects affected / exposed [24]
    1 / 2206 (0.05%)
    0 / 2216 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    3 / 8386 (0.04%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Asthma
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial disorder
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    22 / 8386 (0.26%)
    11 / 8374 (0.13%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chronic respiratory failure
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    10 / 8386 (0.12%)
    13 / 8374 (0.16%)
         occurrences causally related to treatment / all
    1 / 13
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    7 / 8386 (0.08%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal turbinate hypertrophy
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal swelling
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    8 / 8386 (0.10%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 8386 (0.01%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    5 / 8386 (0.06%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Sinus disorder
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conversion disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    4 / 8386 (0.05%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Factitious disorder
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Personality disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device battery issue
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary dyskinesia
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    8 / 8386 (0.10%)
    8 / 8374 (0.10%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    5 / 8386 (0.06%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystocholangitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    8 / 8386 (0.10%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-alcoholic fatty liver
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose decreased
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure decreased
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure diastolic decreased
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac stress test abnormal
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram abnormal
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart rate abnormal
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis C virus test positive
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio abnormal
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio decreased
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    5 / 8386 (0.06%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress echocardiogram abnormal
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial injury
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain herniation
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burns second degree
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac function disturbance postoperative
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ventricle collapse
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary vascular graft occlusion
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye injury
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    6 / 8386 (0.07%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    4 / 8386 (0.05%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal anastomotic leak
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Heat exhaustion
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    5 / 8386 (0.06%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Humerus fracture
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 8386 (0.00%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mallet finger
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery restenosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post concussion syndrome
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural oedema
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative delirium
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative thoracic procedure complication
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural hypertension
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    4 / 8386 (0.05%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 8386 (0.01%)
    7 / 8374 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Seroma
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin abrasion
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    3 / 8386 (0.04%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tendon injury
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    2 / 8386 (0.02%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular bypass dysfunction
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft occlusion
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava injury
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hereditary haemorrhagic telangiectasia
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    11 / 8386 (0.13%)
    8 / 8374 (0.10%)
         occurrences causally related to treatment / all
    0 / 11
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    40 / 8386 (0.48%)
    29 / 8374 (0.35%)
         occurrences causally related to treatment / all
    3 / 42
    0 / 31
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    Angina pectoris
         subjects affected / exposed
    73 / 8386 (0.87%)
    52 / 8374 (0.62%)
         occurrences causally related to treatment / all
    0 / 76
    0 / 55
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    65 / 8386 (0.78%)
    84 / 8374 (1.00%)
         occurrences causally related to treatment / all
    2 / 73
    0 / 90
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arteriosclerosis coronary artery
         subjects affected / exposed
    2 / 8386 (0.02%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    27 / 8386 (0.32%)
    32 / 8374 (0.38%)
         occurrences causally related to treatment / all
    1 / 29
    0 / 42
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    3 / 8386 (0.04%)
    9 / 8374 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    7 / 8386 (0.08%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    8 / 8386 (0.10%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac discomfort
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorder
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    21 / 8386 (0.25%)
    19 / 8374 (0.23%)
         occurrences causally related to treatment / all
    1 / 23
    0 / 20
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    24 / 8386 (0.29%)
    32 / 8374 (0.38%)
         occurrences causally related to treatment / all
    0 / 27
    1 / 40
         deaths causally related to treatment / all
    0 / 0
    1 / 4
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    30 / 8386 (0.36%)
    31 / 8374 (0.37%)
         occurrences causally related to treatment / all
    0 / 31
    0 / 32
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Coronary artery dissection
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 8386 (0.01%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    5 / 8386 (0.06%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart valve incompetence
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    4 / 8386 (0.05%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microvascular coronary artery disease
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    35 / 8386 (0.42%)
    32 / 8374 (0.38%)
         occurrences causally related to treatment / all
    1 / 37
    1 / 34
         deaths causally related to treatment / all
    0 / 7
    1 / 2
    Myocardial ischaemia
         subjects affected / exposed
    6 / 8386 (0.07%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    6 / 8386 (0.07%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular dysfunction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    4 / 8386 (0.05%)
    9 / 8374 (0.11%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Axonal neuropathy
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal ganglia haemorrhage
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid arteriosclerosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery disease
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    14 / 8386 (0.17%)
    8 / 8374 (0.10%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cauda equina syndrome
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral artery occlusion
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral venous thrombosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    3 / 8386 (0.04%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chorea
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cubital tunnel syndrome
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    8 / 8386 (0.10%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    4 / 8386 (0.05%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic cerebral infarction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemic coma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraventricular haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    20 / 8386 (0.24%)
    28 / 8374 (0.33%)
         occurrences causally related to treatment / all
    1 / 21
    0 / 31
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 8386 (0.00%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbosacral radiculopathy
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    0 / 8386 (0.00%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post stroke epilepsy
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    4 / 8386 (0.05%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    3 / 8386 (0.04%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    17 / 8386 (0.20%)
    13 / 8374 (0.16%)
         occurrences causally related to treatment / all
    0 / 17
    1 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalamus haemorrhage
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    21 / 8386 (0.25%)
    19 / 8374 (0.23%)
         occurrences causally related to treatment / all
    0 / 21
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular dementia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo CNS origin
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 8386 (0.07%)
    8 / 8374 (0.10%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemorrhagic anaemia
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness unilateral
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eustachian tube dysfunction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    3 / 8386 (0.04%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Angle closure glaucoma
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lens dislocation
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular fibrosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic ischaemic neuropathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 8386 (0.01%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal exudates
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia obstructive
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 8386 (0.01%)
    7 / 8374 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal polyp
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal prolapse
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendix disorder
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic pseudo-obstruction
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Constipation
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastric perforation
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 8386 (0.06%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal polyp haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingival bleeding
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    10 / 8386 (0.12%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal strangulation
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising colitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal spasm
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    5 / 8386 (0.06%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer perforation
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary gland enlargement
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Short-bowel syndrome
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal stenosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis mesenteric vessel
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tongue oedema
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcerative gastritis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cutaneous vasculitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis allergic
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Petechiae
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash generalised
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin necrosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin reaction
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    14 / 8386 (0.17%)
    18 / 8374 (0.21%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute prerenal failure
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urethral
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis noninfective
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic nephropathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    6 / 8386 (0.07%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cortical necrosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 8386 (0.02%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Renal impairment
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal ischaemia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stag horn calculus
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress urinary incontinence
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    2 / 8386 (0.02%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral obstruction
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary bladder haemorrhage
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid mass
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    6 / 8386 (0.07%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    5 / 8386 (0.06%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone lesion
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic arthropathy
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gouty arthritis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    4 / 8386 (0.05%)
    6 / 8374 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Knee deformity
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    4 / 8386 (0.05%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle tightness
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    10 / 8386 (0.12%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    22 / 8386 (0.26%)
    18 / 8374 (0.21%)
         occurrences causally related to treatment / all
    0 / 22
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    6 / 8386 (0.07%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    2 / 8386 (0.02%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigger finger
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall abscess
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    2 / 8386 (0.02%)
    7 / 8374 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    8 / 8374 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis infective
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis infective staphylococcal
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbuncle
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    11 / 8386 (0.13%)
    13 / 8374 (0.16%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis of male external genital organ
    Additional description: This is gender specific event.
         subjects affected / exposed [25]
    1 / 6180 (0.02%)
    0 / 6158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Creutzfeldt-Jakob disease
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermo-hypodermitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    4 / 8386 (0.05%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    5 / 8386 (0.06%)
    7 / 8374 (0.08%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysematous pyelonephritis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis bacterial
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis enterococcal
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    4 / 8386 (0.05%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    3 / 8386 (0.04%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis viral
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 8386 (0.04%)
    9 / 8374 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haematoma infection
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site infection
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected bite
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected fistula
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected seroma
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 8386 (0.02%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection viral
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lyme disease
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    8 / 8386 (0.10%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis bacterial
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis chronic
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Penile infection
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    34 / 8386 (0.41%)
    39 / 8374 (0.47%)
         occurrences causally related to treatment / all
    1 / 34
    0 / 41
         deaths causally related to treatment / all
    0 / 4
    0 / 3
    Pneumonia bacterial
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural cellulitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural pneumonia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic abscess
    Additional description: This is gender specific event.
         subjects affected / exposed [26]
    0 / 6180 (0.00%)
    1 / 6158 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 8386 (0.01%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyomyositis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    7 / 8386 (0.08%)
    8 / 8374 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Sepsis syndrome
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    2 / 8386 (0.02%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Skin candida
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    2 / 8386 (0.02%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    2 / 8386 (0.02%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superinfection
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 8386 (0.04%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    15 / 8386 (0.18%)
    13 / 8374 (0.16%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    3 / 8386 (0.04%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral sepsis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visceral leishmaniasis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    7 / 8386 (0.08%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    4 / 8386 (0.05%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    2 / 8386 (0.02%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes with hyperosmolarity
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fluid overload
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 8386 (0.00%)
    2 / 8374 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    5 / 8386 (0.06%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperosmolar hyperglycaemic state
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 8386 (0.01%)
    3 / 8374 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    2 / 8386 (0.02%)
    5 / 8374 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    3 / 8386 (0.04%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 8386 (0.01%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Insulin-requiring type 2 diabetes mellitus
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    0 / 8386 (0.00%)
    1 / 8374 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    4 / 8386 (0.05%)
    4 / 8374 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitamin B12 deficiency
         subjects affected / exposed
    1 / 8386 (0.01%)
    0 / 8374 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    [26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects.
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Bococizumab (PF-04950615) Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2015 / 8386 (24.03%)
    1570 / 8374 (18.75%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    270 / 8386 (3.22%)
    303 / 8374 (3.62%)
         occurrences all number
    280
    317
    Nervous system disorders
    Headache
         subjects affected / exposed
    171 / 8386 (2.04%)
    136 / 8374 (1.62%)
         occurrences all number
    189
    160
    General disorders and administration site conditions
    Injection site reaction
         subjects affected / exposed
    588 / 8386 (7.01%)
    88 / 8374 (1.05%)
         occurrences all number
    1949
    188
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    169 / 8386 (2.02%)
    133 / 8374 (1.59%)
         occurrences all number
    197
    157
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    208 / 8386 (2.48%)
    197 / 8374 (2.35%)
         occurrences all number
    224
    224
    Back pain
         subjects affected / exposed
    217 / 8386 (2.59%)
    203 / 8374 (2.42%)
         occurrences all number
    227
    211
    Myalgia
         subjects affected / exposed
    170 / 8386 (2.03%)
    160 / 8374 (1.91%)
         occurrences all number
    186
    190
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    283 / 8386 (3.37%)
    289 / 8374 (3.45%)
         occurrences all number
    317
    308
    Upper respiratory tract infection
         subjects affected / exposed
    183 / 8386 (2.18%)
    193 / 8374 (2.30%)
         occurrences all number
    204
    213
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    217 / 8386 (2.59%)
    195 / 8374 (2.33%)
         occurrences all number
    217
    196

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Oct 2014
    1. An efficacy endpoint of any stroke (fatal and non-fatal), of any etiology which included hemorrhagic stroke, was added. 2. More frequent visits for assessment of direct LDL-C and AEs/serious AEs, for subjects who have had investigational product dose frequency modifications to quater 4 week so that the data monitoring committee can monitor more closely, lipid levels in subjects with a history of low levels of LDL-C during the trial was added. 3. Depression assessments was added so as to capture baseline risk for the disorder, given that depression was found fairly frequently in subjects at high risk of cardiovascular events and its presence might alter performance on the planned cognitive assessments. 4. Health care utilization assessments and endpoints was added to evaluate the potential impact of bococizumab on health care resource utilization. 5. Screening laboratory tests, hs-CRP and Lp(a) was added for subjects who had not had a prior cardiovascular event, since these were established risk factors for the occurrence of cardiovascular events. 6. Safety section was modified to clarify further, how serious adverse events were to be reported.
    12 Feb 2016
    1. Clinical secondary objectives and endpoints were updated to reflect an upgrading of the secondary endpoint of a composite endpoint of all-cause death, non-fatal MI and non-fatal stroke to a key secondary endpoint, in consideration of its clinical importance. The secondary endpoint of nominal change in hs-CRP was changed to percent change in hs-CRP. 2. The proposed indication was modified so that the major cardiovascular events reflected components of the primary endpoint. 3. The safety reporting section was revised to reflect the fact that a Pfizer internal serious adverse event triage group will ensure the correct reporting of serious AEs to the Pfizer Drug Safety Unit. 4. The cerebral hemorrhage risk exclusion was modified to clarify that a prior lacunar infarct refers to a prior lacunar stroke, ie, a lacunar infarct which resulted in a stroke. 5. An exclusion criterion of gastric bypass surgery was added, since its presence could complicate the interpretation of metabolic efficacy and safety data. 6. A requirement was added to the protocol that IP should not be administered, if a subject was prescribed a marketed proprotein convertase subtilisin/kexin type 9 inhibitor during the conduct of the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    01 Nov 2016
    The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents. These indicated that bococizumab was not likely to provide value to patients, physicians, or shareholders. The decision was not based on a recommendation by the independent Data Monitoring Committee to stop the program.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    As specified in SAP, due to discontinuation of the bococizumab clinical development program, health care resource utilization (HCRU) endpoints were not evaluated.
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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