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    Clinical Trial Results:
    A Clinical Outcomes Study to Evaluate the Effects of IL-6 Receptor Blockade With Tocilizumab (TCZ) in Comparison With Etanercept (ETA) on the Rate of Cardiovascular Events in Patients With Moderate to Severe Rheumatoid Arthritis (RA)

    Summary
    EudraCT number
    		 2010-020065-24
    Trial protocol
    		 GB   HU   LV   BE   AT   LT   CZ   DE   ES   NL   GR   IT  
    Global end of trial date
    25 Mar 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Jun 2017
    First version publication date
    29 Jun 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    WA25204
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel,, Switzerland,
    Public contact
    Medical Communications, Hoffmann-La Roche, genentech@druginfo.com
    Scientific contact
    Medical Communications, Hoffmann-La Roche, genentech@druginfo.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
    25 Mar 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    25 Mar 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare prospectively in patients treated with TCZ or ETA, the time to first occurrence of any component of the composite of: • Cardiovascular (CV) death • Non-fatal myocardial infarction (MI) • Non-fatal stroke of all classifications (ischemic, hemorrhagic, or undetermined origin)
    Protection of trial subjects
    The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice. Approval from the Independent Ethics Committee/Institutional Review Board was obtained before study start and was documented in a letter to the Investigator specifying the date on which the committee met and granted the approval.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Aug 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 313
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    Belgium: 15
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 58
    Country: Number of subjects enrolled
    Canada: 79
    Country: Number of subjects enrolled
    Chile: 124
    Country: Number of subjects enrolled
    Czech Republic: 206
    Country: Number of subjects enrolled
    Germany: 65
    Country: Number of subjects enrolled
    Ecuador: 40
    Country: Number of subjects enrolled
    Spain: 88
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    United Kingdom: 62
    Country: Number of subjects enrolled
    Greece: 14
    Country: Number of subjects enrolled
    Croatia: 40
    Country: Number of subjects enrolled
    Hungary: 54
    Country: Number of subjects enrolled
    India: 31
    Country: Number of subjects enrolled
    Italy: 18
    Country: Number of subjects enrolled
    Lithuania: 38
    Country: Number of subjects enrolled
    Latvia: 41
    Country: Number of subjects enrolled
    Mexico: 335
    Country: Number of subjects enrolled
    Malaysia: 18
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Philippines: 21
    Country: Number of subjects enrolled
    Poland: 215
    Country: Number of subjects enrolled
    Romania: 149
    Country: Number of subjects enrolled
    Russian Federation: 206
    Country: Number of subjects enrolled
    Serbia: 64
    Country: Number of subjects enrolled
    Turkey: 10
    Country: Number of subjects enrolled
    United States: 671
    Country: Number of subjects enrolled
    South Africa: 59
    Country: Number of subjects enrolled
    Israel: 21
    Worldwide total number of subjects
    3080
    EEA total number of subjects
    1030
    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)
    2182
    From 65 to 84 years
    895
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 3080 patients were enrolled from 353 sites, across 31 countries

    Pre-assignment
    Screening details
    		 The target population was patients with moderate to severe rheumatoid arthritis ≥ 6 months duration and for whom non-biologic DMARD treatment or treatment with an anti-tumor necrosis factor (anti-TNF) agent was inadequate. Patients were required to be 50 years or older and to have at least one additional CV risk factor beyond RA.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tocilizumab
    Arm description
    		 Participants received 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    RoActemra, Actemra, RO4877533
    Pharmaceutical forms
    Solution for injection/infusion in pre-filled syringe
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tocilizumab was administered at a dose of 8 mg/kg every 4 weeks.

    Arm title
    		 Etanercept
    Arm description
    		 Participants received 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Etanercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received 50 mg etanercept subcutaneously weekly

    Number of subjects in period 1
    		Tocilizumab Etanercept
    Started
    1538
    1542
    Completed
    1482
    1475
    Not completed
    56
    67
         Adverse event, serious fatal
    30
    34
         Consent withdrawn by subject
    13
    16
         Info not recorded
    10
    16
         Lost to follow-up
    3
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tocilizumab
    Reporting group description
    		 Participants received 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.

    Reporting group title
    Etanercept
    Reporting group description
    		 Participants received 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.

    Reporting group values
    		 Tocilizumab Etanercept Total
    Number of subjects
    		 1538 1542 3080
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 1095 1087 2182
        From 65-84 years
    		 441 454 895
        85 years and over
    		 2 1 3
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 60.7 ( 7.4 ) 60.7 ( 7.6 ) -
    Gender, Male/Female
    Units: Participants
        Female
    		 1193 1202 2395
        Male
    		 345 340 685

    End points

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    End points reporting groups
    Reporting group title
    Tocilizumab
    Reporting group description
    		 Participants received 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.

    Reporting group title
    Etanercept
    Reporting group description
    		 Participants received 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.

    Primary: Time to first Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event

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    End point title
    		 Time to first Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event
    End point description
    Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Primary
    End point timeframe
    Baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentage of patients with event
        number (not applicable)
    5.4
    5.1
    Statistical analysis title
    		 Cox Regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative MACE rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.43
    Notes
    [1] - In order to reject the null hypothesis and claim non-inferiority of TCZ compared to ETA, a HR point estimate of ≤ 1.278 and upper limit of 95% CI <1.8 was required.

    Primary: Time to first CV-EAC Adjudicated Event - Sensitivity Analysis

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    End point title
    		 Time to first CV-EAC Adjudicated Event - Sensitivity Analysis
    End point description
    Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Primary
    End point timeframe
    From Baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentage of patients with event
        number (not applicable)
    3.7
    3.4
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the OT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative MACE rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.62
    Notes
    [2] - The non-inferiority margin was only formally tested for the primary ITT analysis and not for the sensitivity analysis.

    Primary: Time to first CV-EAC adjudicated event excluding undetermined cause of death - Sensitivity Analysis

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    End point title
    		 Time to first CV-EAC adjudicated event excluding undetermined cause of death - Sensitivity Analysis
    End point description
    Prospective comparison of time to first occurrence of any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Primary
    End point timeframe
    From baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentage of patients with an event
        number (not applicable)
    4.8
    4.7
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative MACE rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.4
    Notes
    [3] - The non-inferiority margin was only formally tested for the primary ITT analysis and not for the sensitivity analysis.

    Primary: Time to first CV-EAC adjudicated event before last direct contact date - Sensitivity Analysis

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    End point title
    		 Time to first CV-EAC adjudicated event before last direct contact date - Sensitivity Analysis
    End point description
    Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call). Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Primary
    End point timeframe
    From Baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentage of participants with an event
        number (not applicable)
    3.2
    3
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative MACE rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.56
    Notes
    [4] - The non-inferiority margin was only formally tested for the primary ITT analysis and not for the sensitivity analysis.

    Secondary: The time to first occurrence of an expanded CV composite endpoint

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    End point title
    		 The time to first occurrence of an expanded CV composite endpoint
    End point description
    Prospective comparison of the time to first ccurrence of the expanded composite endpoint. The expanded composite endpoint is defined as the CV composite of the primary endpoint with the addition of non-elective coronary revascularization procedures and hospitalization for unstable angina. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Secondary
    End point timeframe
    From baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentages of participants
        number (not applicable)
    5.5
    5.4
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.34
    Notes
    [5] - The non-inferiority margin was only formally tested for the primary ITT analysis

    Secondary: Individual component of primary endpoint: Non-fatal Myocardial Infarction

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    End point title
    		 Individual component of primary endpoint: Non-fatal Myocardial Infarction
    End point description
    Prospective comparison of time to first occurrence of Individual component of primary endpoint: Non fatal Myocardial Infarction. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Secondary
    End point timeframe
    From baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentage of participants
        number (not applicable)
    1.8
    2
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.49
    Notes
    [6] - The non-inferiority margin was only formally tested for the primary ITT analysis

    Secondary: Individual component of primary endpoint: cardiovascular death

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    End point title
    		 Individual component of primary endpoint: cardiovascular death
    End point description
    Prospective comparison of time to first occurrence of Individual component of primary endpoint: cardiovascular death. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Secondary
    End point timeframe
    From baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentage of participants
        number (not applicable)
    2.3
    2.3
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.63
    Notes
    [7] - The non-inferiority margin was only formally tested for the primary ITT analysis.

    Secondary: Individual component of primary endpoint: non-fatal stroke

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    End point title
    		 Individual component of primary endpoint: non-fatal stroke
    End point description
    Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal stroke. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Secondary
    End point timeframe
    From baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percentage of participants with an event
        number (not applicable)
    1.6
    1
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 2.92
    Notes
    [8] - The non-inferiority margin was only formally tested for the primary ITT analysis

    Secondary: Individual component of primary endpoint: All-cause mortality

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    End point title
    		 Individual component of primary endpoint: All-cause mortality
    End point description
    Prospective comparison of time to first occurrence of Individual component of primary endpoint: All-cause mortality. Median time to event and 95% confidence intervals could not be estimated due to less than 50% of patients experiencing an event; percentage of patients with event is reported.
    End point type
    Secondary
    End point timeframe
    From baseline up to 4.9 years
    End point values
    		 Tocilizumab Etanercept
    Number of subjects analysed
    1538
    1542
    Units: Percenntage of participants
        number (not applicable)
    4.2
    4.2
    Statistical analysis title
    		 Cox regression
    Statistical analysis description
    The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients. A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata: • Previous exposure to anti-TNF (Yes/No) • History of CV events (Yes/No)
    Comparison groups
    Tocilizumab v Etanercept
    Number of subjects included in analysis
    3080
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.41
    Notes
    [9] - The non-inferiority margin was only formally tested for the primary ITT analysis.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected throughout the entire course of the study.
    Adverse event reporting additional description
    Analyses were conducted on the On treatment safety (OTS) population.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Etanercept
    Reporting group description
    		 Participants received 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.

    Reporting group title
    Tocilizumab
    Reporting group description
    		 Participants received 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.

    Serious adverse events
    		 Etanercept Tocilizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    422 / 1542 (27.37%)
    479 / 1538 (31.14%)
         number of deaths (all causes)
    69
    67
         number of deaths resulting from adverse events
    10
    14
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ADENOCARCINOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ADENOCARCINOMA OF COLON
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANAL SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BASAL CELL CARCINOMA
         subjects affected / exposed
    3 / 1542 (0.19%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BENIGN ANORECTAL NEOPLASM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BENIGN NEOPLASM OF CERVIX UTERI
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BLADDER TRANSITIONAL CELL CARCINOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BLADDER CANCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    BRAIN NEOPLASM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    BREAST CANCER
         subjects affected / exposed
    3 / 1542 (0.19%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    CARCINOID TUMOUR OF THE GASTROINTESTINAL TRACT
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARCINOID TUMOUR PULMONARY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC MYXOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CENTRAL NERVOUS SYSTEM LYMPHOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL HAEMANGIOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLANGIOCARCINOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    COLON ADENOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLON CANCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLON CANCER METASTATIC
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    COLORECTAL CANCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIFFUSE LARGE B−CELL LYMPHOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENDOMETRIAL ADENOCARCINOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GLIOBLASTOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMANGIOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTESTINAL ADENOCARCINOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTRADUCTAL PROLIFERATIVE BREAST LESION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LARYNGEAL CANCER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUNG ADENOCARCINOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    LUNG ADENOCARCINOMA STAGE IV
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    LUNG CANCER METASTATIC
         subjects affected / exposed
    2 / 1542 (0.13%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    LUNG NEOPLASM
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    LUNG NEOPLASM MALIGNANT
         subjects affected / exposed
    4 / 1542 (0.26%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 2
    1 / 3
    MALIGNANT MELANOMA STAGE II
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MARJOLIN’S ULCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTASES TO BONE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTATIC GASTRIC CANCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    METASTATIC NEOPLASM
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    NEOPLASM MALIGNANT
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NON−HODGKIN’S LYMPHOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OVARIAN ADENOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OVARIAN CANCER
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    PANCREATIC CARCINOMA METASTATIC
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    PANCREATIC NEOPLASM
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    PAPILLARY THYROID CANCER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PARAPROTEINAEMIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PHARYNGEAL NEOPLASM BENIGN
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PARATHYROID TUMOUR BENIGN
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PITUITARY TUMOUR BENIGN
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLASMA CELL MYELOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PROSTATE CANCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL CANCER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL CELL CARCINOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SMALL CELL LUNG CANCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF LUNG
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF THE TONGUE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SQUAMOUS ENDOMETRIAL CARCINOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    THYROID ADENOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TONGUE NEOPLASM MALIGNANT STAGE UNSPECIFIED
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TUMOUR INVASION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UTERINE CANCER
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vascular disorders
    AORTIC ANEURYSM
         subjects affected / exposed
    4 / 1542 (0.26%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    AORTIC ANEURYSM RUPTURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    AORTIC CALCIFICATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    AORTIC DISSECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    AORTIC STENOSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    8 / 1542 (0.52%)
    6 / 1538 (0.39%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMBOLISM ARTERIAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMORAL ARTERY EMBOLISM
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMATOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    6 / 1542 (0.39%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSIVE CRISIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSIVE EMERGENCY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFARCTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL ISCHAEMIA
         subjects affected / exposed
    2 / 1542 (0.13%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL VENOUS DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RHEUMATOID VASCULITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUBCLAVIAN ARTERY OCCLUSION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    THROMBOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VARICOSE VEIN
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VENOUS THROMBOSIS LIMB
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    ABDOMINAL HERNIA REPAIR
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANAL FISTULA EXCISION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANGIOPLASTY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    APPENDICECTOMY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC PACEMAKER REPLACEMENT
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLOSTOMY CLOSURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HIP ARTHROPLASTY
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    IMPLANTABLE DEFIBRILLATOR INSERTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    KNEE ARTHROPLASTY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LARGE INTESTINE ANASTOMOSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MITRAL VALVE REPLACEMENT
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEQUESTRECTOMY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UMBILICAL HERNIA REPAIR
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    CHEST PAIN
         subjects affected / exposed
    10 / 1542 (0.65%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COMPLICATION ASSOCIATED WITH DEVICE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    4 / 1542 (0.26%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 4
    0 / 3
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    IMPAIRED HEALING
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOCAL SWELLING
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MULTIPLE ORGAN DYSFUNCTION SYNDROME
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    NON−CARDIAC CHEST PAIN
         subjects affected / exposed
    1 / 1542 (0.06%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    PYREXIA
         subjects affected / exposed
    3 / 1542 (0.19%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUDDEN DEATH
         subjects affected / exposed
    1 / 1542 (0.06%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    SWELLING
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERSENSITIVITY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OVERLAP SYNDROME
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SARCOIDOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    ACQUIRED PHIMOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BREAST FIBROSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CERVICAL POLYP
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CERVICAL DYSPLASIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CYSTOCELE
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GENITAL PROLAPSE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METRORRHAGIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OVARIAN CYST
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OVARIAN CYST TORSION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPERMATOCELE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RECTOCELE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UTERINE POLYP
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UTERINE PROLAPSE
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VAGINAL HAEMATOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE PULMONARY OEDEMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ALVEOLITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASTHMA
         subjects affected / exposed
    5 / 1542 (0.32%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASTHMATIC CRISIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATELECTASIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHIAL HYPERREACTIVITY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHIAL OBSTRUCTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS CHRONIC
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHOSPASM
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHOSTENOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    7 / 1542 (0.45%)
    10 / 1538 (0.65%)
         occurrences causally related to treatment / all
    2 / 7
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    CHRONIC RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    4 / 1542 (0.26%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMPHYSEMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EPISTAXIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYDROTHORAX
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOXIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    3 / 1542 (0.19%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUNG DISORDER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUNG INFILTRATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    5 / 1542 (0.32%)
    6 / 1538 (0.39%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    11 / 1542 (0.71%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    2 / 11
    0 / 1
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    PULMONARY FIBROSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    PULMONARY GRANULOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY HYPERTENSION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY MASS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY OEDEMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY SARCOIDOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY THROMBOSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    RESPIRATORY DISTRESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    6 / 1542 (0.39%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 1
         deaths causally related to treatment / all
    1 / 3
    0 / 0
    Psychiatric disorders
    BURNOUT SYNDROME
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CONFUSIONAL STATE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DELIRIUM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DELIRIUM TREMENS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEPRESSION
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MAJOR DEPRESSION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MENTAL DISORDER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MENTAL STATUS CHANGES
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PSYCHOTIC DISORDER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SCHIZOAFFECTIVE DISORDER BIPOLAR TYPE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUICIDAL IDEATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUICIDE ATTEMPT
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MANIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    DEVICE BREAKAGE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEVICE DISLOCATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEVICE FAILURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEVICE LOOSENING
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    BILE DUCT OBSTRUCTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLANGITIS ACUTE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLECYSTITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLECYSTITIS CHRONIC
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    6 / 1542 (0.39%)
    14 / 1538 (0.91%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATIC VEIN THROMBOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATITIS ACUTE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    POST CHOLECYSTECTOMY SYNDROME
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    EOSINOPHIL COUNT INCREASED
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMATOCRIT ABNORMAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMOGLOBIN ABNORMAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LIVER FUNCTION TEST INCREASED
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STAPHYLOCOCCUS TEST POSITIVE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SYNOVIAL FLUID WHITE BLOOD CELLS POSITIVE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSAMINASES INCREASED
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TROPONIN INCREASED
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ACCIDENT AT WORK
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ANAEMIA POSTOPERATIVE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANKLE FRACTURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ARTHROPOD STING
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    COMMINUTED FRACTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CONTUSION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DISLOCATION OF VERTEBRA
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    FALL
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMORAL NECK FRACTURE
         subjects affected / exposed
    3 / 1542 (0.19%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    6 / 1542 (0.39%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FOOT FRACTURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FRACTURE DISPLACEMENT
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GUN SHOT WOUND
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    HAND FRACTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    12 / 1542 (0.78%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    4 / 1542 (0.26%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFUSION RELATED REACTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    JOINT DISLOCATION
         subjects affected / exposed
    2 / 1542 (0.13%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    JOINT INJURY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LIGAMENT INJURY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (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
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OVERDOSE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PATELLA FRACTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMOTHORAX TRAUMATIC
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    POST PROCEDURAL FISTULA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    POST PROCEDURAL HAEMATOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RADIUS FRACTURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY FUME INHALATION DISORDER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RIB FRACTURE
         subjects affected / exposed
    4 / 1542 (0.26%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPINAL FRACTURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STOMAL HERNIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STRESS FRACTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUBCUTANEOUS HAEMATOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUBDURAL HAEMATOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SYNOVIAL RUPTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TENDON RUPTURE
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    THORACIC VERTEBRAL FRACTURE
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ULNA FRACTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UPPER LIMB FRACTURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WOUND
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WOUND DEHISCENCE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         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
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    ATRIAL SEPTAL DEFECT
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         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 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE CORONARY SYNDROME
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    9 / 1542 (0.58%)
    7 / 1538 (0.46%)
         occurrences causally related to treatment / all
    1 / 9
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ADAMS−STOKES SYNDROME
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANGINA PECTORIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    8 / 1538 (0.52%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANGINA UNSTABLE
         subjects affected / exposed
    7 / 1542 (0.45%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 10
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    18 / 1542 (1.17%)
    14 / 1538 (0.91%)
         occurrences causally related to treatment / all
    3 / 23
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIAL FLUTTER
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK SECOND DEGREE
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRADYARRHYTHMIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRADYCARDIA
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BUNDLE BRANCH BLOCK LEFT
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    4 / 1542 (0.26%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    CARDIAC FAILURE
         subjects affected / exposed
    3 / 1542 (0.19%)
    11 / 1538 (0.72%)
         occurrences causally related to treatment / all
    0 / 3
    5 / 16
         deaths causally related to treatment / all
    0 / 1
    1 / 3
    CARDIAC FAILURE CHRONIC
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    8 / 1542 (0.52%)
    7 / 1538 (0.46%)
         occurrences causally related to treatment / all
    2 / 11
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    CARDIAC FIBRILLATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC TAMPONADE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIOGENIC SHOCK
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIOMYOPATHY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIOPULMONARY FAILURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    3 / 1542 (0.19%)
    9 / 1538 (0.59%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CORONARY ARTERY OCCLUSION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CORONARY ARTERY STENOSIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSIVE HEART DISEASE
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ISCHAEMIC CARDIOMYOPATHY
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    MITRAL VALVE INCOMPETENCE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (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
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    15 / 1542 (0.97%)
    10 / 1538 (0.65%)
         occurrences causally related to treatment / all
    2 / 15
    0 / 10
         deaths causally related to treatment / all
    1 / 5
    0 / 1
    MYOCARDIAL ISCHAEMIA
         subjects affected / exposed
    3 / 1542 (0.19%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    PALPITATIONS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    POSTINFARCTION ANGINA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SILENT MYOCARDIAL INFARCTION
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SINOATRIAL BLOCK
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SINUS BRADYCARDIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SINUS NODE DYSFUNCTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TACHYCARDIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VENTRICULAR DYSFUNCTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VENTRICULAR FIBRILLATION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (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
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIO−RESPIRATORY ARREST
         subjects affected / exposed
    3 / 1542 (0.19%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    1 / 3
    0 / 1
    Nervous system disorders
    AMYOTROPHIC LATERAL SCLEROSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BALANCE DISORDER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRAIN STEM INFARCTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CAROTID ARTERY DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CAROTID ARTERY STENOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL HAEMATOMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL ISCHAEMIA
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL INFARCTION
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    8 / 1542 (0.52%)
    14 / 1538 (0.91%)
         occurrences causally related to treatment / all
    0 / 8
    2 / 15
         deaths causally related to treatment / all
    0 / 3
    1 / 3
    CEREBROVASCULAR DISORDER
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CERVICAL CORD COMPRESSION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         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
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    DEMENTIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEMENTIA ALZHEIMER’S TYPE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    DIABETIC COMA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSKINESIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSARTHRIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMBOLIC STROKE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENCEPHALOPATHY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EPILEPSY
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FACIAL PARALYSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GENERALISED TONIC−CLONIC SEIZURE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMORRHAGIC STROKE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    HEMIPARESIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATIC ENCEPHALOPATHY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSIVE ENCEPHALOPATHY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         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
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    5 / 1542 (0.32%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    LOSS OF CONSCIOUSNESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUMBAR RADICULOPATHY
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METABOLIC ENCEPHALOPATHY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MIGRAINE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYASTHENIA GRAVIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PARAESTHESIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PARKINSON’S DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (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
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    REVERSIBLE ISCHAEMIC NEUROLOGICAL DEFICIT
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RUPTURED CEREBRAL ANEURYSM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SCIATICA
         subjects affected / exposed
    3 / 1542 (0.19%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPINAL CORD COMPRESSION
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    SUBARACHNOID HAEMORRHAGE
         subjects affected / exposed
    3 / 1542 (0.19%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    SYNCOPE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSIENT GLOBAL AMNESIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    3 / 1542 (0.19%)
    9 / 1538 (0.59%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VASCULAR DEMENTIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    9 / 1542 (0.58%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    AUTOIMMUNE HAEMOLYTIC ANAEMIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COAGULOPATHY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GRANULOCYTOPENIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LEUKOCYTOSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MICROCYTIC ANAEMIA
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    4 / 1542 (0.26%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LEUKOPENIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    DEAFNESS UNILATERAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VERTIGO
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         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
    2 / 1542 (0.13%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CORNEAL PERFORATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    KERATITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         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
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RETINAL DETACHMENT
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SCLERITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ULCERATIVE KERATITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL ADHESIONS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL HERNIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    4 / 1542 (0.26%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACID PEPTIC DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACUTE ABDOMEN
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ASCITES
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLITIS ISCHAEMIC
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLITIS ULCERATIVE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CROHN’S DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIAPHRAGMATIC HERNIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    4 / 1542 (0.26%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIVERTICULAR PERFORATION
         subjects affected / exposed
    1 / 1542 (0.06%)
    6 / 1538 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIVERTICULUM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIVERTICULUM INTESTINAL
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIVERTICULUM INTESTINAL HAEMORRHAGIC
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DUODENAL ULCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENTERITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENTEROCOLITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMORAL HERNIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         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
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRIC ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRIC ULCER PERFORATION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRITIS HAEMORRHAGIC
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    4 / 1542 (0.26%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    GASTROINTESTINAL INFLAMMATION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROINTESTINAL ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMATEMESIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    HAEMATOCHEZIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INCARCERATED HIATUS HERNIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INCARCERATED UMBILICAL HERNIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INGUINAL HERNIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LARGE INTESTINAL STENOSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         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
    0 / 1542 (0.00%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LARGE INTESTINE POLYP
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOWER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MALLORY−WEISS SYNDROME
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MELAENA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OESOPHAGITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PALATAL DISORDER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    3 / 1542 (0.19%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    PEPTIC ULCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PEPTIC ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RETROPERITONEAL FIBROSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    2 / 1542 (0.13%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    VOMITING
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    ANGIOEDEMA
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BLISTER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DECUBITUS ULCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DERMAL CYST
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DERMATITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIABETIC FOOT
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERSENSITIVITY VASCULITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    PEMPHIGOID
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RASH
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RASH ERYTHEMATOUS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SKIN DISORDER
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SKIN NECROSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SKIN ULCER
         subjects affected / exposed
    1 / 1542 (0.06%)
    4 / 1538 (0.26%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URTICARIA
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VASCULITIC ULCER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    5 / 1542 (0.32%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CALCULUS BLADDER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CALCULUS URINARY
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHRONIC KIDNEY DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CYSTITIS HAEMORRHAGIC
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    END STAGE RENAL DISEASE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    GLOMERULONEPHRITIS CHRONIC
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYDRONEPHROSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    3 / 1542 (0.19%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OBSTRUCTIVE NEPHROPATHY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PELVI−URETERIC OBSTRUCTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL COLIC
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    3 / 1542 (0.19%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TUBULOINTERSTITIAL NEPHRITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URETERIC OBSTRUCTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URETEROLITHIASIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URETHRAL STENOSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    GOITRE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTHYROIDISM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOTHYROIDISM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ARTHRITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    6 / 1542 (0.39%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BURSITIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COSTOCHONDRITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FASCIITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FINGER DEFORMITY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FISTULA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FOOT DEFORMITY
         subjects affected / exposed
    3 / 1542 (0.19%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMARTHROSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC DISORDER
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC PROTRUSION
         subjects affected / exposed
    6 / 1542 (0.39%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    KNEE DEFORMITY
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LIMB DEFORMITY
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUMBAR SPINAL STENOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MORPHOEA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCLE SPASMS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYALGIA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NECK PAIN
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEOARTHRITIS
         subjects affected / exposed
    22 / 1542 (1.43%)
    14 / 1538 (0.91%)
         occurrences causally related to treatment / all
    0 / 24
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEONECROSIS
         subjects affected / exposed
    4 / 1542 (0.26%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEONECROSIS OF JAW
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEOPOROSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEOPOROTIC FRACTURE
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIARTHRITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RHEUMATOID ARTHRITIS
         subjects affected / exposed
    15 / 1542 (0.97%)
    12 / 1538 (0.78%)
         occurrences causally related to treatment / all
    0 / 19
    2 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RHEUMATOID NODULE
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ROTATOR CUFF SYNDROME
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPINAL OSTEOARTHRITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPONDYLOLISTHESIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SYNOVIAL CYST
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TENOSYNOVITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SYNOVITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABSCESS LIMB
         subjects affected / exposed
    0 / 1542 (0.00%)
    6 / 1538 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABSCESS ORAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABSCESS RUPTURE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACUTE SINUSITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANAL ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ARTHRITIS BACTERIAL
         subjects affected / exposed
    6 / 1542 (0.39%)
    9 / 1538 (0.59%)
         occurrences causally related to treatment / all
    5 / 7
    3 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ARTHRITIS INFECTIVE
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASPERGILLUS INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATYPICAL PNEUMONIA
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BILIARY SEPSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    4 / 1542 (0.26%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS VIRAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHOPULMONARY ASPERGILLOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BURSITIS INFECTIVE
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    8 / 1542 (0.52%)
    24 / 1538 (1.56%)
         occurrences causally related to treatment / all
    5 / 8
    13 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CELLULITIS STAPHYLOCOCCAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CELLULITIS STREPTOCOCCAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CERVICITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHRONIC TONSILLITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLONIC ABSCESS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DENGUE FEVER
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEVICE RELATED SEPSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DISSEMINATED TUBERCULOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    10 / 1538 (0.65%)
         occurrences causally related to treatment / all
    1 / 1
    5 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMPYEMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENDOPHTHALMITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENTERITIS INFECTIOUS
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EPIDIDYMITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EPIGLOTTITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ERYSIPELAS
         subjects affected / exposed
    2 / 1542 (0.13%)
    11 / 1538 (0.72%)
         occurrences causally related to treatment / all
    3 / 4
    3 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ESCHERICHIA PYELONEPHRITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ESCHERICHIA SEPSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ESCHERICHIA URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FUNGAL SKIN INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    6 / 1542 (0.39%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    2 / 6
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS NOROVIRUS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GROIN ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMATOMA INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMOPHILUS SEPSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HERPANGINA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    4 / 1542 (0.26%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTED DERMAL CYST
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTIOUS COLITIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTIOUS PLEURAL EFFUSION
         subjects affected / exposed
    1 / 1542 (0.06%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTIVE ANEURYSM
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INJECTION SITE ABSCESS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTERVERTEBRAL DISCITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOCALISED INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUDWIG ANGINA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUNG ABSCESS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUNG INFECTION PSEUDOMONAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MASTOIDITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MENINGITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCLE ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NASAL ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUROSYPHILIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OESOPHAGEAL CANDIDIASIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OPHTHALMIC HERPES SIMPLEX
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OPHTHALMIC HERPES ZOSTER
         subjects affected / exposed
    1 / 1542 (0.06%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEOMYELITIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEOMYELITIS CHRONIC
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OTITIS EXTERNA
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PAPILLOMA VIRAL INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIHEPATIC ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERITONITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    PERITONSILLAR ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PHARYNGITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMOCYSTIS JIROVECII PNEUMONIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    41 / 1542 (2.66%)
    47 / 1538 (3.06%)
         occurrences causally related to treatment / all
    18 / 46
    20 / 53
         deaths causally related to treatment / all
    0 / 6
    4 / 8
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    PNEUMONIA INFLUENZAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA MYCOPLASMAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA PNEUMOCOCCAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA STAPHYLOCOCCAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA VIRAL
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    POST PROCEDURAL INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND INFECTION
         subjects affected / exposed
    4 / 1542 (0.26%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PSEUDOMONAS INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY TUBERCULOMA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY TUBERCULOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RECTAL ABSCESS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    2 / 1542 (0.13%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SALPINGITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SCROTAL ABSCESS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    7 / 1542 (0.45%)
    6 / 1538 (0.39%)
         occurrences causally related to treatment / all
    2 / 7
    2 / 6
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    3 / 1542 (0.19%)
    3 / 1538 (0.20%)
         occurrences causally related to treatment / all
    3 / 4
    2 / 3
         deaths causally related to treatment / all
    1 / 2
    2 / 3
    SINUSITIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SOFT TISSUE INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STAPHYLOCOCCAL SEPSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STREPTOCOCCAL BACTERAEMIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUBCUTANEOUS ABSCESS
         subjects affected / exposed
    3 / 1542 (0.19%)
    2 / 1538 (0.13%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TONGUE ABSCESS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TONSILLITIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TOXIC SHOCK SYNDROME STREPTOCOCCAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRACHEITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TUBERCULOSIS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    12 / 1542 (0.78%)
    7 / 1538 (0.46%)
         occurrences causally related to treatment / all
    6 / 13
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION BACTERIAL
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    2 / 1542 (0.13%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIRAL PHARYNGITIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WEST NILE VIRAL INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WOUND INFECTION
         subjects affected / exposed
    1 / 1542 (0.06%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    4 / 1542 (0.26%)
    5 / 1538 (0.33%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIABETES MELLITUS
         subjects affected / exposed
    0 / 1542 (0.00%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIABETIC COMPLICATION
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    ELECTROLYTE IMBALANCE
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERGLYCAEMIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERKALAEMIA
         subjects affected / exposed
    3 / 1542 (0.19%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    3 / 1542 (0.19%)
    1 / 1538 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METABOLIC ACIDOSIS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TYPE 2 DIABETES MELLITUS
         subjects affected / exposed
    1 / 1542 (0.06%)
    0 / 1538 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Etanercept Tocilizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    910 / 1542 (59.01%)
    1090 / 1538 (70.87%)
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    44 / 1542 (2.85%)
    120 / 1538 (7.80%)
         occurrences all number
    48
    156
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    158 / 1542 (10.25%)
    200 / 1538 (13.00%)
         occurrences all number
    178
    268
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    68 / 1542 (4.41%)
    103 / 1538 (6.70%)
         occurrences all number
    79
    132
    Blood and lymphatic system disorders
    LEUKOPENIA
         subjects affected / exposed
    21 / 1542 (1.36%)
    85 / 1538 (5.53%)
         occurrences all number
    32
    128
    NEUTROPENIA
         subjects affected / exposed
    33 / 1542 (2.14%)
    92 / 1538 (5.98%)
         occurrences all number
    49
    153
    Gastrointestinal disorders
    DIARRHOEA
         subjects affected / exposed
    84 / 1542 (5.45%)
    140 / 1538 (9.10%)
         occurrences all number
    94
    182
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    76 / 1542 (4.93%)
    127 / 1538 (8.26%)
         occurrences all number
    87
    147
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    106 / 1542 (6.87%)
    143 / 1538 (9.30%)
         occurrences all number
    166
    209
    BACK PAIN
         subjects affected / exposed
    92 / 1542 (5.97%)
    147 / 1538 (9.56%)
         occurrences all number
    104
    176
    RHEUMATOID ARTHRITIS
         subjects affected / exposed
    132 / 1542 (8.56%)
    152 / 1538 (9.88%)
         occurrences all number
    179
    246
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    185 / 1542 (12.00%)
    244 / 1538 (15.86%)
         occurrences all number
    249
    337
    NASOPHARYNGITIS
         subjects affected / exposed
    141 / 1542 (9.14%)
    239 / 1538 (15.54%)
         occurrences all number
    181
    386
    PHARYNGITIS
         subjects affected / exposed
    76 / 1542 (4.93%)
    113 / 1538 (7.35%)
         occurrences all number
    98
    146
    SINUSITIS
         subjects affected / exposed
    78 / 1542 (5.06%)
    88 / 1538 (5.72%)
         occurrences all number
    103
    124
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    193 / 1542 (12.52%)
    243 / 1538 (15.80%)
         occurrences all number
    291
    425
    URINARY TRACT INFECTION
         subjects affected / exposed
    150 / 1542 (9.73%)
    174 / 1538 (11.31%)
         occurrences all number
    200
    243
    Metabolism and nutrition disorders
    HYPERCHOLESTEROLAEMIA
         subjects affected / exposed
    52 / 1542 (3.37%)
    143 / 1538 (9.30%)
         occurrences all number
    55
    158

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jan 2011
    - Removal of the interim analysis - Inclusion of stroke of all classifications - "Premature withdrawal" and "Minimal telephone follow up upon withdrawal from active participation" related info were split in two different sections - Hypersensitivity reactions and Immunogenicity assessment: treatment recommendations were removed from the protocol to allow health care providers to include all therapies available according to the standard of care appropriate for the patient’s reaction - Decision about monitoring compliance with home-administered etanercept to be assessed using Interactive Voice Response System (IVRS) and used syringe counts. - Revision of the process for identifying and reporting cardiovascular events for adjudication - Sponsor's decision not to collect biomarkers
    21 Mar 2014
    - The study sample size was increased by 10% (from 2,800 to 3,080 patients) following a written recommendation from the Steering Committee - Addition of check mark for liver profile at screening in the schedule of assessments - Clarification of the non requirement for patients who withdraw from active study participation but consent to minimal follow up (e.g., annual telephone follow up) to sign a separate ICF - Treatments that are listed as “prohibited” were listed as “strongly discouraged” instead - Clear definition of the differences between (i) discontinuing study drug, (ii) discontinuing active study participation, and (iii) completely withdrawing from the study - Inclusion of additional detail to the End of Study section including description of the Common Study End Date - Inclusion of a clear indication about which assessments are required at the yearly visits for patients who have discontinued randomized treatment - Clarification about the collection requirement limited to SAEs and CV events in patients on non-randomized treatment; AEs and AESIs do not need to be collected in these patients unless they are receiving TCZ - Clarification about the fact that fully diluted Tocilizumab solutions for infusion are only stable at room temperature for a maximum of 6 hours - Volume of infusion determined by the current body weight, obtained at each visit prior to TCZ administration, rather than the last recorded body weight - Inclusion into the schedule of assessments of the following statement: subjects must have Swollen joint count (SJC) ≥ 8 (66 joint count) and tender joint count (TJC) ≥ 8 (68 joint count) during screening or at the baseline visit for enrollment

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

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

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