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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effect of Long-Term Treatment with BELVIQ (lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects with Cardiovascular Disease or Multiple Cardiovascular Risk Factors

    Summary
    EudraCT number
    2013-000324-34
    Trial protocol
    PL  
    Global end of trial date
    14 May 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    13 Jul 2019
    First version publication date
    30 May 2019
    Other versions
    v1
    Version creation reason
    • Changes to summary attachments
    Updates to be made in the time frame of 2 endpoints and 1 analysis population description.

    Trial information

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    Trial identification
    Sponsor protocol code
    APD356-G000-401
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02019264
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Eisai Ltd.
    Sponsor organisation address
    European Knowledge Centre, Mosquito Way, Hatfield, Hertfordshire, United Kingdom, AL10 9SN
    Public contact
    Eisai Medical Information, Eisai Ltd., +1 888-274-2378, esi_medinfo@eisai.com
    Scientific contact
    Eisai Medical Information, Eisai Ltd., +1 888-274-2378, esi_medinfo@eisai.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 May 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 May 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that, in obese and overweight subjects with cardiovascular (CV) disease and/or multiple CV risk factors, lorcaserin hydrochloride (HCl) 10 milligram (mg) administered twice daily (BID) does not increase the incidence of major adverse cardiovascular events (MACE) (myocardial infarction [MI], or stroke, or CV death) compared to placebo, with a noninferiority margin for the hazard ratio (HR) of 1.4, and in obese and overweight subjects with CV disease and/or multiple CV risk factors, lorcaserin HCl 10 mg BID reduces the incidence of MACE+ (MACE or hospitalization for unstable angina or heart failure [HF], or any coronary revascularization) compared to placebo
    Protection of trial subjects
    This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    24 Jan 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 8627
    Country: Number of subjects enrolled
    Australia: 535
    Country: Number of subjects enrolled
    Bahamas: 10
    Country: Number of subjects enrolled
    Canada: 1165
    Country: Number of subjects enrolled
    Chile: 107
    Country: Number of subjects enrolled
    Mexico: 255
    Country: Number of subjects enrolled
    New Zealand: 316
    Country: Number of subjects enrolled
    Poland: 985
    Worldwide total number of subjects
    12000
    EEA total number of subjects
    985
    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)
    6257
    From 65 to 84 years
    5699
    85 years and over
    44

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects took part in the study at investigative sites in the United States, Bahamas, Canada, Mexico, Chile, New Zealand, Poland, and Australia from 24 Jan 2014 to 14 May 2018.

    Pre-assignment
    Screening details
    A total of 14,673 subjects were screened and enrolled, of which 2673 subjects were screen failures and 12,000 were randomized to receive lorcaserin HCl or placebo.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Subjects received lorcaserin HCL placebo-matching, tablets, orally, twice daily for up to 52 months.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Lorcaserin HCL placebo-matching, tablets, orally, twice daily for up to 52 months.

    Arm title
    Lorcaserin 10 mg
    Arm description
    Subjects received lorcaserin HCL 10 mg, tablets, orally, twice daily for up to 52 months.
    Arm type
    Experimental

    Investigational medicinal product name
    Lorcaserin
    Investigational medicinal product code
    Other name
    APD356, BELVIQ
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Lorcaserin HCL 10 mg, tablets, orally, twice daily for up to 52 months.

    Number of subjects in period 1
    Placebo Lorcaserin 10 mg
    Started
    6000
    6000
    Completed
    5752
    5793
    Not completed
    248
    207
         Missing
    14
    11
         Administrative reason
    36
    28
         Not Treated
    6
    4
         Withdrawal by subjects
    142
    117
         Lost to follow-up
    50
    47

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received lorcaserin HCL placebo-matching, tablets, orally, twice daily for up to 52 months.

    Reporting group title
    Lorcaserin 10 mg
    Reporting group description
    Subjects received lorcaserin HCL 10 mg, tablets, orally, twice daily for up to 52 months.

    Reporting group values
    Placebo Lorcaserin 10 mg Total
    Number of subjects
    6000 6000 12000
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.7 ± 8.31 63.5 ± 8.33 -
    Gender categorical
    Units: Subjects
        Female
    2186 2112 4298
        Male
    3814 3888 7702
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    536 502 1038
        Not Hispanic or Latino
    5464 5498 10962
        Unknown or Not Reported
    0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    21 26 47
        Asian
    74 85 159
        Native Hawaiian or Other Pacific Islander
    23 30 53
        Black or African American
    466 454 920
        White
    5331 5309 10640
        More than one race
    85 96 181
        Unknown or Not Reported
    0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received lorcaserin HCL placebo-matching, tablets, orally, twice daily for up to 52 months.

    Reporting group title
    Lorcaserin 10 mg
    Reporting group description
    Subjects received lorcaserin HCL 10 mg, tablets, orally, twice daily for up to 52 months.

    Primary: Time From Randomization to First Occurrence of Major Adverse Cardiovascular Events (MACE) at Interim Analysis

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    End point title
    Time From Randomization to First Occurrence of Major Adverse Cardiovascular Events (MACE) at Interim Analysis
    End point description
    The MACE events involved MI, stroke, or CV death. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The total time analysis set using the intent-to-treat (ITT) set, events were counted that occurred while subjects were on and off treatment. Subjects with no events were censored at their last study contact or at the visit following sponsor notification of study completion, whichever occurred first. Here "99999" refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Primary
    End point timeframe
    Baseline up to Month 42
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    6000
    6000
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    P-value
    < 0.0001
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.005
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    0.842
         upper limit
    1.198
    Notes
    [1] - Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates. MACE met non-inferiority when the one-sided upper bound of 97.5% confidence interval of the HR was less than (<) 1.4 (the non-inferiority margin).

    Primary: Time From Randomization to First Occurrence of MACE+

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    End point title
    Time From Randomization to First Occurrence of MACE+
    End point description
    The MACE+ events involved MI, stroke, or CV death or hospitalization for unstable angina or heart failure (HF), or any coronary revascularization. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The total time analysis set used the ITT set, events were counted that occurred while subjects were on and off treatment. Subjects with no events were censored at their last study contact or at the visit following Sponsor Notification of Study Completion, whichever occurred first. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Primary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    6000
    6000
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.5464
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.969
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.873
         upper limit
    1.074
    Notes
    [2] - Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates.

    Secondary: Time From Randomization to Conversion to Type 2 Diabetes Mellitus (T2DM) for Subjects With Prediabetes at Baseline

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    End point title
    Time From Randomization to Conversion to Type 2 Diabetes Mellitus (T2DM) for Subjects With Prediabetes at Baseline
    End point description
    Time from randomization to conversion to T2DM was defined as first occurrence of any component of the 2013 American Diabetes Association (ADA) Diagnostic Criteria (ADA, 2013) in subjects with prediabetes at baseline. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. Prediabetes and total time analysis set used ITT set: without a history of any type of diabetes and who were prediabetic at baseline; events were counted that occurred while subjects were on, off treatment; subjects with no events were censored at last study contact/at visit after notification of study completion, whichever occurred first. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    1976
    2015
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    3991
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.038
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.807
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.659
         upper limit
    0.988
    Notes
    [3] - Hazard ratio was based on Cox-regression model including treatment as covariate.

    Secondary: Time From Randomization to First Occurrence of the Individual Components of MACE+

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    End point title
    Time From Randomization to First Occurrence of the Individual Components of MACE+
    End point description
    The MACE+ events involved MI, stroke, or CV death or hospitalization for unstable angina or HF, or any coronary revascularization. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The total time analysis set used the ITT set, events counted occurred while subjects were on and off treatment. Subjects with no events were censored at last study contact or at the visit following Sponsor Notification of Study Completion, whichever first. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    6000
    6000
    Units: days
    arithmetic mean (confidence interval 95%)
        MI
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Stroke
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        CV death
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Hospitalization for unstable angina
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        HF
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Coronary revascularization
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [4]
    P-value
    = 0.0001
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.991
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    0.824
         upper limit
    1.191
    Notes
    [4] - MI: Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates. 97.5% confidence interval refers to the upper limit of the displayed 2-sided 95% confidence interval.
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [5]
    P-value
    = 0.0005
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.856
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    0.639
         upper limit
    1.145
    Notes
    [5] - Time to Stroke: Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates. 97.5% confidence interval refers to the upper limit of the displayed 2-sided 95% confidence interval.
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [6]
    P-value
    = 0.0262
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.045
    Confidence interval
         level
    97.5%
         sides
    2-sided
         lower limit
    0.778
         upper limit
    1.404
    Notes
    [6] - Cardiovascular Death: Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates. 97.5% confidence interval refers to the upper limit of the displayed 2-sided 95% confidence interval.
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    superiority [7]
    P-value
    = 0.3243
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.163
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.861
         upper limit
    1.571
    Notes
    [7] - Hospitalization for Unstable Angina: Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates.
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    superiority [8]
    P-value
    = 0.6758
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.952
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.757
         upper limit
    1.197
    Notes
    [8] - HF: Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates.
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    superiority [9]
    P-value
    = 0.7817
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.981
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.856
         upper limit
    1.125
    Notes
    [9] - Coronary Revascularization: Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates.

    Secondary: Time From Randomization to Event of All-cause Mortality

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    End point title
    Time From Randomization to Event of All-cause Mortality
    End point description
    The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The total time analysis set used the ITT set, events were counted that occurred while subjects were on and off treatment. Subjects with no events were censored at their last study contact or at the visit following Sponsor Notification of Study Completion, whichever occurred first. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    6000
    6000
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4212
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.082
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.893
         upper limit
    1.31

    Secondary: Time From Randomization to Conversion to Normal Glucose Homeostasis in Subjects With Prediabetes at Baseline

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    End point title
    Time From Randomization to Conversion to Normal Glucose Homeostasis in Subjects With Prediabetes at Baseline
    End point description
    Normal glucose homeostasis was defined as glycosylated hemoglobin (HbA1c) less than or equal to (<=) 5.6% and fasting plasma glucose (FPG) < 100 milligram per deciliter (mg/dL) without any antidiabetic treatment. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The prediabetes analysis set included all subjects in the ITT set without a history of any type of diabetes and who were prediabetic at baseline. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    1976
    2015
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    3991
    Analysis specification
    Pre-specified
    Analysis type
    superiority [10]
    P-value
    = 0.181
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.124
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.947
         upper limit
    1.333
    Notes
    [10] - Hazard ratio was based on a Cox regression model including treatment as covariate.

    Secondary: Time From Randomization to Conversion to T2DM for Subjects Without Any Type of Diabetes at Baseline

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    End point title
    Time From Randomization to Conversion to T2DM for Subjects Without Any Type of Diabetes at Baseline
    End point description
    The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The nondiabetes analysis set included all subjects in the ITT set without a history of any type of diabetes at baseline. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    2569
    2615
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    5184
    Analysis specification
    Pre-specified
    Analysis type
    superiority [11]
    P-value
    = 0.0116
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.773
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.633
         upper limit
    0.944
    Notes
    [11] - Hazard ratio was based on a Cox regression model including treatment as covariate.

    Secondary: Change From Baseline in HbA1c at Month 6 in Subjects With T2DM at Baseline

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    End point title
    Change From Baseline in HbA1c at Month 6 in Subjects With T2DM at Baseline
    End point description
    The T2DM analysis set included all subjects in the ITT set who had T2DM at baseline. Here "n" was the T2DM analysis set where data was available at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, and Month 6
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    3403
    3362
    Units: percentage of HbA1c
    arithmetic mean (standard deviation)
        Baseline (n=3403, 3362)
    6.99 ± 1.066
    7.01 ± 1.082
        Change at Month 6 (n=3087, 3035)
    0.06 ± 0.777
    -0.33 ± 0.785
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    6765
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [12]
    Method
    ANCOVA
    Parameter type
    Least square (LS) Mean Difference (Net)
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.43
         upper limit
    -0.35
    Notes
    [12] - P-value was based on analysis of covariance (ANCOVA) model with treatment and stratification variable (presence of established CV disease or CV risk factors without established CV disease) as factors, and baseline HbA1c, as a covariate.

    Secondary: Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in All Subjects

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    End point title
    Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in All Subjects
    End point description
    New onset/worsening of existing renal impairment was first occurrence of any events: microalbuminuria and macroalbuminuria, worsening albuminuria (microalbuminuria at Baseline developed macroalbuminuria, ACR increased >=30% from Baseline during treatment), newly developed chronic kidney disease (CKD) or worsening of CKD (based on National Kidney Foundation [NKF] Guidelines [2002]) worsened to higher CKD stages during treatment), or doubling of serum creatinine (creatinine value at least 2 times Baseline value and >=1.5 mg/dL during treatment.), or any of following: end-stage renal disease, renal transplant, renal death. Outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. ITT set included all randomized subjects regardless of whether they took study drug or not. This set was the same as full analysis set. "99999": Median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    6000
    6000
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    12000
    Analysis specification
    Pre-specified
    Analysis type
    superiority [13]
    P-value
    = 0.0054
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.869
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.787
         upper limit
    0.959
    Notes
    [13] - Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates.

    Secondary: Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Subjects With Prediabetes at Baseline

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    End point title
    Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Subjects With Prediabetes at Baseline
    End point description
    New onset/worsening of existing renal impairment was first occurrence of any events: microalbuminuria and macroalbuminuria, worsening albuminuria (microalbuminuria at Baseline developed macroalbuminuria, ACR increased >=30% from baseline during treatment),CKD as per NKF Guidelines [2002]) or worsening of CKD (CKD Stage1/higher as per NKF Guidelines [2002] worsened to higher CKD stages during treatment), or doubling serum creatinine(creatinine value at least twice baseline value and >=1.5 mg/dL during treatment.), or any of: end stage renal disease, renal transplant, renal death. Outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. ITT set included all subjects without a history of any type of diabetes and were prediabetic at baseline. This set was the same as full analysis set. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    1976
    2015
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    3991
    Analysis specification
    Pre-specified
    Analysis type
    superiority [14]
    P-value
    = 0.3661
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.904
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.727
         upper limit
    1.125
    Notes
    [14] - Hazard ratio on a Cox regression model including treatment as covariate.

    Secondary: Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Subjects With T2DM at Baseline

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    End point title
    Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Subjects With T2DM at Baseline
    End point description
    New onset/worsening of existing renal impairment was first occurrence of any events: microalbuminuria and macroalbuminuria, worsening albuminuria (microalbuminuria at baseline developed macroalbuminuria, ACR increased>=30% from baseline during treatment), CKD as per NKF Guidelines [2002]) or worsening of CKD (CKD Stage 1/higher as per NKF Guidelines [2002] worsened to higher CKD stages during treatment), or doubling of serum creatinine (creatinine value at least 2 times baseline value and>=1.5 mg/dL during treatment.), or any of the following: end-stage renal disease, renal transplant, renal death. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The T2DM analysis set had all subjects in the ITT set who had T2DM at baseline. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    3403
    3362
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    6765
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0082
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.855
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.762
         upper limit
    0.96

    Secondary: Time From Randomization to Event of Improvement in Renal Function in Subjects With T2DM at Baseline

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    End point title
    Time From Randomization to Event of Improvement in Renal Function in Subjects With T2DM at Baseline
    End point description
    Improvement in renal function: first occurrence of regression of albuminuria/regression of CKD. Regression of albuminuria: when subjects with macroalbuminuria at baseline developed microalbuminuria or nonalbuminuria, or subjects with microalbuminuria at baseline became nonalbuminuric, and ACR value decreased >= 30% from previous assessment in treatment. Regression of CKD: when subjects with CKD Stage 1/higher at baseline improved to normal/lower stages by NKF guidelines in treatment. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula. The T2DM analysis set included all subjects in ITT set who had T2DM at baseline. Here “99999” refers to median time and 95% confidence interval which could not be calculated since quartile was not estimable due to higher number of censored subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Month 56)
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    3403
    3362
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    6765
    Analysis specification
    Pre-specified
    Analysis type
    superiority [15]
    P-value
    = 0.0297
    Method
    Primary Analytic Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.182
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.017
         upper limit
    1.375
    Notes
    [15] - Hazard ratio was based on Cox-regression model including treatment and CV strata as covariates.

    Secondary: Percentage of Subjects Who Met FDA-Defined Valvulopathy in Echocardiographically Determined Heart Valve Changes

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    End point title
    Percentage of Subjects Who Met FDA-Defined Valvulopathy in Echocardiographically Determined Heart Valve Changes
    End point description
    The FDA-defined valvulopathy analysis set included all subjects in the ITT set without FDA-defined valvulopathy at baseline. Here “n” was the FDA-defined valvulopathy analysis set where data was available at specified time point.
    End point type
    Secondary
    End point timeframe
    Months 6 and 12
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    1935
    1925
    Units: percentage of subjects
    number (not applicable)
        Month 6 (n=1683, 1681)
    1.4
    2.1
        Month 12 (n=1564, 1579)
    1.5
    1.8
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    3860
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5015 [16]
    Method
    Primary Analytic Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    2.11
    Notes
    [16] - P-value was based on logistic regression including treatment as a factor and baseline body mass index (BMI) as a covariate.

    Secondary: Percentage of Subjects With FDA-Defined Valvulopathy at Baseline Who Demonstrated Worsened FDA-Defined Valvulopathy

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    End point title
    Percentage of Subjects With FDA-Defined Valvulopathy at Baseline Who Demonstrated Worsened FDA-Defined Valvulopathy
    End point description
    The ITT analysis set in subjects with FDA-defined valvulopathy at baseline was used. Here “n” was the ITT analysis set in subjects with FDA-defined valvulopathy at baseline where data was available at specified time point.
    End point type
    Secondary
    End point timeframe
    Months 6 and 12
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    228
    225
    Units: percentage of subjects
    number (not applicable)
        Month 6 (n=194, 201)
    2.1
    3.5
        Month 12 (n=180, 189)
    1.7
    2.1
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Placebo v Lorcaserin 10 mg
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7249 [17]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.29
         upper limit
    5.98
    Notes
    [17] - P-value was based on logistic regression including treatment as a factor and baseline BMI as a covariate.

    Secondary: Change From Baseline in Echocardiographically-Determined Pulmonary Arterial Systolic Pressure

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    End point title
    Change From Baseline in Echocardiographically-Determined Pulmonary Arterial Systolic Pressure
    End point description
    The ITT analysis set-subjects in ECHO substudy included all randomized subjects regardless of whether they took study drug or not. Here "n" was the ITT analysis set-subjects in the ECHO substudy, where data was available at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    Placebo Lorcaserin 10 mg
    Number of subjects analysed
    2167
    2151
    Units: Millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        Baseline (n=1368, 1358)
    26.4354 ± 7.66312
    26.2029 ± 7.54123
        Change at Month 12 (n=882, 893)
    -0.6418 ± 6.81716
    -0.8223 ± 7.23770
    Statistical analysis title
    Placebo, Lorcaserin 10 mg
    Comparison groups
    Lorcaserin 10 mg v Placebo
    Number of subjects included in analysis
    4318
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2976 [18]
    Method
    Mixed-effects model
    Parameter type
    Mean difference (net)
    Point estimate
    -0.9036
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2908
         upper limit
    -0.5163
    Notes
    [18] - P value was based on a mixed-effects model (unstructured covariance matrix) with repeated measures with treatment, month and treatment by month interaction as factors and baseline pulmonary arterial systolic pressure and baseline BMI as covariates.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline up to 30 days after last dose of study drug (approximately 56 months)
    Adverse event reporting additional description
    Adverse events were collected for the subject who were in the safety analysis set (all subjects who received at least 1 dose of study drug and had at least one post dose safety assessment).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received lorcaserin HCL placebo-matching, tablets, orally, twice daily for up to 52 months.

    Reporting group title
    Lorcaserin 10 mg
    Reporting group description
    Subjects received lorcaserin HCL 10 mg, tablets, orally, twice daily for up to 52 months.

    Serious adverse events
    Placebo Lorcaserin 10 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2021 / 5992 (33.73%)
    1974 / 5995 (32.93%)
         number of deaths (all causes)
    202
    219
         number of deaths resulting from adverse events
    121
    132
    Injury, poisoning and procedural complications
    Abdominal injury
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    2 / 5992 (0.03%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic ulcer haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    4 / 5992 (0.07%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial bypass thrombosis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial injury
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder injury
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac contusion
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac valve replacement complication
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cartilage injury
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    2 / 5992 (0.03%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         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 / 5992 (0.02%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    3 / 5992 (0.05%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis radiation
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delayed recovery from anaesthesia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    15 / 5992 (0.25%)
    21 / 5995 (0.35%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    4 / 5992 (0.07%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 5992 (0.03%)
    10 / 5995 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    3 / 5992 (0.05%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal stoma complication
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    2 / 5992 (0.03%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    5 / 5992 (0.08%)
    10 / 5995 (0.17%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    6 / 5992 (0.10%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ilium fracture
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated incisional hernia
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site complication
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site haemorrhage
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incomplete spinal fusion
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal anastomosis complication
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaw fracture
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint capsule rupture
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    3 / 5992 (0.05%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation postoperative
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney contusion
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb traumatic amputation
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver contusion
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes postoperative
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         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 / 5992 (0.02%)
    1 / 5995 (0.02%)
         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
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    3 / 5992 (0.05%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periprosthetic fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis chemical
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post laminectomy syndrome
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural bile leak
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    3 / 5992 (0.05%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Post procedural discharge
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    2 / 5992 (0.03%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    3 / 5992 (0.05%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural myocardial infarction
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural swelling
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative fever
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    1 / 5992 (0.02%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative renal failure
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative thoracic procedure complication
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postpericardiotomy syndrome
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural hypotension
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary contusion
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    9 / 5992 (0.15%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    9 / 5992 (0.15%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    Scapula fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt malfunction
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt occlusion
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin abrasion
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    3 / 5992 (0.05%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Stab wound
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    7 / 5992 (0.12%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic arthritis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    4 / 5992 (0.07%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    4 / 5992 (0.07%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention postoperative
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm ruptured
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weaning failure
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Wound haematoma
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Ammonia increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic bruit
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood calcium decreased
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood immunoglobulin G decreased
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood potassium increased
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood sodium increased
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood urine present
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Body temperature increased
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac stress test abnormal
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulation test abnormal
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ECG signs of myocardial ischaemia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram ST segment depression
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram abnormal
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glycosylated haemoglobin increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart rate decreased
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio abnormal
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (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 increased
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    N-terminal prohormone brain natriuretic peptide increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary arterial pressure increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    8 / 5992 (0.13%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count increased
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    14 / 5992 (0.23%)
    11 / 5995 (0.18%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    3 / 5992 (0.05%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    117 / 5992 (1.95%)
    105 / 5995 (1.75%)
         occurrences causally related to treatment / all
    1 / 131
    0 / 118
         deaths causally related to treatment / all
    1 / 7
    0 / 3
    Angina pectoris
         subjects affected / exposed
    123 / 5992 (2.05%)
    142 / 5995 (2.37%)
         occurrences causally related to treatment / all
    0 / 136
    0 / 152
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    106 / 5992 (1.77%)
    113 / 5995 (1.88%)
         occurrences causally related to treatment / all
    1 / 115
    0 / 129
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Anginal equivalent
         subjects affected / exposed
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    4 / 5992 (0.07%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    1 / 4
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 5992 (0.02%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arteriospasm coronary
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    102 / 5992 (1.70%)
    105 / 5995 (1.75%)
         occurrences causally related to treatment / all
    2 / 122
    3 / 120
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    22 / 5992 (0.37%)
    21 / 5995 (0.35%)
         occurrences causally related to treatment / all
    0 / 28
    3 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 5992 (0.00%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    7 / 5992 (0.12%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    3 / 5992 (0.05%)
    7 / 5995 (0.12%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    17 / 5992 (0.28%)
    18 / 5995 (0.30%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bundle branch block bilateral
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block right
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac aneurysm
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    19 / 5992 (0.32%)
    17 / 5995 (0.28%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 17
         deaths causally related to treatment / all
    0 / 11
    0 / 11
    Cardiac discomfort
         subjects affected / exposed
    7 / 5992 (0.12%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorder
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    21 / 5992 (0.35%)
    18 / 5995 (0.30%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 19
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    5 / 5992 (0.08%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    106 / 5992 (1.77%)
    91 / 5995 (1.52%)
         occurrences causally related to treatment / all
    2 / 139
    3 / 124
         deaths causally related to treatment / all
    1 / 3
    0 / 1
    Cardiac perforation
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    6 / 5992 (0.10%)
    7 / 5995 (0.12%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 7
         deaths causally related to treatment / all
    0 / 5
    1 / 6
    Cardiogenic shock
         subjects affected / exposed
    5 / 5992 (0.08%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 4
         deaths causally related to treatment / all
    1 / 3
    0 / 2
    Cardiomyopathy
         subjects affected / exposed
    4 / 5992 (0.07%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Cardiovascular disorder
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale acute
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale chronic
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    78 / 5992 (1.30%)
    87 / 5995 (1.45%)
         occurrences causally related to treatment / all
    0 / 80
    3 / 92
         deaths causally related to treatment / all
    0 / 0
    0 / 8
    Coronary artery occlusion
         subjects affected / exposed
    6 / 5992 (0.10%)
    8 / 5995 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery perforation
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    13 / 5992 (0.22%)
    17 / 5995 (0.28%)
         occurrences causally related to treatment / all
    0 / 13
    1 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diastolic dysfunction
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperdynamic left ventricle
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intracardiac thrombus
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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 / 5992 (0.07%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kounis syndrome
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left atrial dilatation
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    3 / 5992 (0.05%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microvascular coronary artery disease
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    12 / 5992 (0.20%)
    12 / 5995 (0.20%)
         occurrences causally related to treatment / all
    3 / 12
    4 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve prolapse
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    31 / 5992 (0.52%)
    36 / 5995 (0.60%)
         occurrences causally related to treatment / all
    2 / 31
    0 / 38
         deaths causally related to treatment / all
    1 / 9
    0 / 4
    Myocardial ischaemia
         subjects affected / exposed
    16 / 5992 (0.27%)
    14 / 5995 (0.23%)
         occurrences causally related to treatment / all
    1 / 17
    1 / 14
         deaths causally related to treatment / all
    0 / 0
    1 / 3
    Palpitations
         subjects affected / exposed
    5 / 5992 (0.08%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial cyst
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 5992 (0.00%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis constrictive
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prinzmetal angina
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary valve incompetence
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    Right ventricular failure
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    6 / 5992 (0.10%)
    15 / 5995 (0.25%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Supraventricular tachycardia
         subjects affected / exposed
    9 / 5992 (0.15%)
    11 / 5995 (0.18%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systolic dysfunction
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 5992 (0.02%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    7 / 5992 (0.12%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    3 / 7
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    8 / 5992 (0.13%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Ventricular tachyarrhythmia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    22 / 5992 (0.37%)
    13 / 5995 (0.22%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Choledochal cyst
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Developmental hip dysplasia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal arteriovenous malformation
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocele
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microgenia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    Abdominal lymphadenopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    19 / 5992 (0.32%)
    12 / 5995 (0.20%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia macrocytic
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    7 / 5992 (0.12%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 5992 (0.03%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    3 / 5992 (0.05%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic haematoma
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spontaneous haematoma
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Basal ganglia infarction
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bickerstaff's encephalitis
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    3 / 5992 (0.05%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Brain stem haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem stroke
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery disease
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    17 / 5992 (0.28%)
    15 / 5995 (0.25%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid sinus syndrome
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system necrosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         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 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral circulatory failure
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    4 / 5992 (0.07%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrospinal fluid leakage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    41 / 5992 (0.68%)
    29 / 5995 (0.48%)
         occurrences causally related to treatment / all
    3 / 42
    1 / 31
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Cerebrovascular disorder
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical cord compression
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical myelopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervicogenic headache
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complex partial seizures
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cranial nerve palsies multiple
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cubital tunnel syndrome
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic coma
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    9 / 5992 (0.15%)
    14 / 5995 (0.23%)
         occurrences causally related to treatment / all
    0 / 9
    2 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness postural
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic cerebral infarction
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    2 / 5992 (0.03%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frontal lobe epilepsy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Headache
         subjects affected / exposed
    9 / 5992 (0.15%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    2 / 5992 (0.03%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    5 / 5992 (0.08%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    IIIrd nerve paralysis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    14 / 5992 (0.23%)
    13 / 5995 (0.22%)
         occurrences causally related to treatment / all
    0 / 14
    1 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Lacunar infarction
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    4 / 5992 (0.07%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbosacral radiculopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    2 / 5992 (0.03%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    5 / 5992 (0.08%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine with aura
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Motor neurone disease
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelomalacia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelopathy
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myoclonus
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    0 / 5992 (0.00%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve root compression
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuralgia
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuromyelitis optica spectrum disorder
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 5992 (0.02%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinsonism
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peroneal nerve palsy
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Petit mal epilepsy
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (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
    13 / 5992 (0.22%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radial nerve palsy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radicular pain
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    7 / 5992 (0.12%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    4 / 5992 (0.07%)
    10 / 5995 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Serotonin syndrome
         subjects affected / exposed
    3 / 5992 (0.05%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    4 / 4
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Simple partial seizures
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Slow speech
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal claudication
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord disorder
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylitic myelopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    2 / 5992 (0.03%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Superficial siderosis of central nervous system
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior sagittal sinus thrombosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    49 / 5992 (0.82%)
    54 / 5995 (0.90%)
         occurrences causally related to treatment / all
    3 / 51
    1 / 62
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Thalamus haemorrhage
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    38 / 5992 (0.63%)
    46 / 5995 (0.77%)
         occurrences causally related to treatment / all
    0 / 39
    3 / 55
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transverse sinus thrombosis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 5992 (0.00%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIth nerve paralysis
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery dissection
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery thrombosis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord paralysis
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    3 / 5992 (0.05%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Charles Bonnet syndrome
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deformity of orbit
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular oedema
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oscillopsia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal vascular thrombosis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous adhesions
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Tympanic membrane perforation
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    8 / 5992 (0.13%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    1 / 5992 (0.02%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal discomfort
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal fat apron
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         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
    10 / 5992 (0.17%)
    7 / 5995 (0.12%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia obstructive
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal incarcerated hernia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    11 / 5992 (0.18%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    7 / 5992 (0.12%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal incontinence
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorectal varices
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coeliac artery stenosis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    8 / 5992 (0.13%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis microscopic
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic pseudo-obstruction
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    6 / 5992 (0.10%)
    8 / 5995 (0.13%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    6 / 5992 (0.10%)
    8 / 5995 (0.13%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dieulafoy's vascular malformation
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    4 / 5992 (0.07%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    2 / 5992 (0.03%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenogastric reflux
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    6 / 5992 (0.10%)
    4 / 5995 (0.07%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocele
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive duodenitis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric antral vascular ectasia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric disorder
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastric perforation
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (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 / 5992 (0.00%)
    1 / 5995 (0.02%)
         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
    5 / 5992 (0.08%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    6 / 5992 (0.10%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    3 / 5992 (0.05%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal angiodysplasia haemorrhagic
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    27 / 5992 (0.45%)
    29 / 5995 (0.48%)
         occurrences causally related to treatment / all
    0 / 30
    0 / 29
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Gastrointestinal necrosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal ulcer haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (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
    9 / 5992 (0.15%)
    11 / 5995 (0.18%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    2 / 5992 (0.03%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    5 / 5992 (0.08%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         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
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 5992 (0.02%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    9 / 5992 (0.15%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal dilatation
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (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
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    3 / 5992 (0.05%)
    7 / 5995 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal ulcer
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    2 / 5992 (0.03%)
    5 / 5995 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    9 / 5992 (0.15%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Megacolon
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (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
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric artery stenosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric panniculitis
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    3 / 5992 (0.05%)
    8 / 5995 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Odynophagia
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal food impaction
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal pain
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal spasm
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    2 / 5992 (0.03%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Omental infarction
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    14 / 5992 (0.23%)
    13 / 5995 (0.22%)
         occurrences causally related to treatment / all
    5 / 15
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    15 / 5992 (0.25%)
    9 / 5995 (0.15%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis relapsing
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    6 / 5992 (0.10%)
    8 / 5995 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haemorrhage
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary gland mass
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (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
    18 / 5992 (0.30%)
    11 / 5995 (0.18%)
         occurrences causally related to treatment / all
    0 / 22
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue disorder
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    7 / 5992 (0.12%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 5992 (0.08%)
    3 / 5995 (0.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uvulitis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visceroptosis
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    7 / 5992 (0.12%)
    6 / 5995 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    57 / 5992 (0.95%)
    57 / 5995 (0.95%)
         occurrences causally related to treatment / all
    1 / 64
    0 / 61
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Acute prerenal failure
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Albuminuria
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder disorder
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder dysfunction
         subjects affected / exposed
    0 / 5992 (0.00%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder neck obstruction
         subjects affected / exposed
    3 / 5992 (0.05%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder necrosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder outlet obstruction
         subjects affected / exposed
    0 / 5992 (0.00%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder prolapse
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder stenosis
         subjects affected / exposed
    1 / 5992 (0.02%)
    0 / 5995 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    5 / 5992 (0.08%)
    2 / 5995 (0.03%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic nephropathy
         subjects affected / exposed
    1 / 5992 (0.02%)
    1 / 5995 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0