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    Clinical Trial Results:
    A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects with Type 2 Diabetes and Nephropathy. SONAR: Study Of Diabetic Nephropathy with Atrasentan

    Summary
    EudraCT number
    		 2012-005848-21
    Trial protocol
    		 SE   DE   CZ   BE   GB   IE   PT   DK   NL   IT   GR   SK   FI   ES   PL   AT  
    Global end of trial date
    29 Mar 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Apr 2019
    First version publication date
    14 Apr 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    M11-352
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01858532
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co. KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Services, AbbVie, 001 800-633-9110,
    Scientific contact
    Melissa Wigderson, AbbVie, melissa.wigderson@abbvie.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
    29 Mar 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Mar 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The study objective was to evaluate the effect of atrasentan compared with placebo on time to doubling of serum creatinine (DBSC) or the onset of end-stage renal disease (ESRD) in adults with type 2 diabetes and nephropathy who were treated with the maximum tolerated labeled daily dose (MTLDD) of a renin-angiotensin system (RAS) inhibitor. The study also assessed cardiovascular (CV) morbidity and mortality, urine albumin excretion, and changes in estimated glomerular filtration rate (eGFR). There was an optional Pre-Screening Period, Screening Period, Run-In Period (up to 12 weeks), Enrichment Period (6 weeks of atrasentan Tx), Double-Blind Treatment Period (randomization to final Tx visit), and Follow-Up Period (Final Tx to F1 visit [45 days post Tx] and other post-treatment visits). The study was prematurely discontinued because of a lower than expected event rate for the renal composite endpoint, which was adjudicated by a blinded independent events adjudication committee.
    Protection of trial subjects
    Prior to the initiation of any screening or study-specific procedures, the investigator or his or her representative explained the nature of the study to the subject or his or her representative and answered all questions regarding this study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 May 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 62
    Country: Number of subjects enrolled
    Australia: 56
    Country: Number of subjects enrolled
    Austria: 14
    Country: Number of subjects enrolled
    Belgium: 22
    Country: Number of subjects enrolled
    Brazil: 259
    Country: Number of subjects enrolled
    Canada: 74
    Country: Number of subjects enrolled
    Chile: 40
    Country: Number of subjects enrolled
    China: 283
    Country: Number of subjects enrolled
    Czech Republic: 66
    Country: Number of subjects enrolled
    Denmark: 28
    Country: Number of subjects enrolled
    Finland: 12
    Country: Number of subjects enrolled
    France: 48
    Country: Number of subjects enrolled
    Germany: 79
    Country: Number of subjects enrolled
    Greece: 38
    Country: Number of subjects enrolled
    Hong Kong: 135
    Country: Number of subjects enrolled
    Ireland: 25
    Country: Number of subjects enrolled
    Israel: 82
    Country: Number of subjects enrolled
    Italy: 166
    Country: Number of subjects enrolled
    Japan: 386
    Country: Number of subjects enrolled
    Korea, Republic of: 234
    Country: Number of subjects enrolled
    Malaysia: 195
    Country: Number of subjects enrolled
    Mexico: 149
    Country: Number of subjects enrolled
    Netherlands: 41
    Country: Number of subjects enrolled
    New Zealand: 45
    Country: Number of subjects enrolled
    Peru: 111
    Country: Number of subjects enrolled
    Poland: 56
    Country: Number of subjects enrolled
    Portugal: 38
    Country: Number of subjects enrolled
    Puerto Rico: 132
    Country: Number of subjects enrolled
    Romania: 49
    Country: Number of subjects enrolled
    Russian Federation: 164
    Country: Number of subjects enrolled
    Singapore: 33
    Country: Number of subjects enrolled
    Slovakia: 65
    Country: Number of subjects enrolled
    South Africa: 64
    Country: Number of subjects enrolled
    Spain: 315
    Country: Number of subjects enrolled
    Sweden: 8
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    Taiwan: 141
    Country: Number of subjects enrolled
    Turkey: 19
    Country: Number of subjects enrolled
    Ukraine: 111
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    United States: 1237
    Worldwide total number of subjects
    5107
    EEA total number of subjects
    1094
    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)
    2473
    From 65 to 84 years
    2621
    85 years and over
    13

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 5107 participants dosed in the Enrichment Period (EP); 1441 prematurely discontinued Tx or did not proceed to the Double-Blind Treatment Period per criteria. 3666 participants completed EP and proceeded to Double-Blind Treatment Period, along with 2 additional participants who discontinued study drug in EP but were randomized in error.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Intent-to-Treat (ITT) Responder atrasentan
    Arm description
    		 Participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive atrasentan in the Double-Blind Treatment Period
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atrasentan
    Investigational medicinal product code
    Other name
    ABT-627
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    0.75 mg atrasentan once daily by mouth for 48 months

    Arm title
    		 Intent-to-Treat (ITT) Responder placebo
    Arm description
    		 Participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive placebo in the Double-Blind Treatment Period
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo once daily by mouth for 48 months

    Arm title
    		 Intent-to-Treat (ITT) Non-responder atrasentan
    Arm description
    		 Participants who achieved < 30% reduction in their urinary albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive atrasentan in the Double-Blind Treatment Period
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atrasentan
    Investigational medicinal product code
    Other name
    ABT-627
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    0.75 mg atrasentan once daily by mouth for 48 months

    Arm title
    		 Intent-to-Treat (ITT) Non-responder placebo
    Arm description
    		 Participants who achieved < 30% reduction in their urinary albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive placebo in the Double-Blind Treatment Period
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo once daily by mouth for 48 months

    Number of subjects in period 1 [1]
    		Intent-to-Treat (ITT) Responder atrasentan Intent-to-Treat (ITT) Responder placebo Intent-to-Treat (ITT) Non-responder atrasentan Intent-to-Treat (ITT) Non-responder placebo
    Started
    1325
    1323
    509
    511
    Completed
    1144
    1131
    411
    418
    Not completed
    181
    192
    98
    93
         Adverse event, non-fatal
    58
    50
    23
    28
         Other, not specified
    29
    15
    13
    11
         Lost to follow-up
    17
    26
    11
    14
         Withdrew consent
    71
    93
    46
    27
         Deterioration of medical status
    3
    4
    3
    7
         Investigator request
    3
    4
    2
    6
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 5107 subjects dosed in the open-label Enrichment Period (EP). Of these, 1441 either prematurely discontinued study treatment during the EP or were unable to proceed to the Double-Blind Treatment Period per protocol-specified criteria. 3,666 subjects completed the EP and proceeded into the Double-Blind Treatment Period, along with 2 additional subjects who discontinued study drug in the EP but were randomized in error, for a total of 3,668 subjects.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Intent-to-Treat (ITT) Responder atrasentan
    Reporting group description
    		 Participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive atrasentan in the Double-Blind Treatment Period

    Reporting group title
    Intent-to-Treat (ITT) Responder placebo
    Reporting group description
    		 Participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive placebo in the Double-Blind Treatment Period

    Reporting group title
    Intent-to-Treat (ITT) Non-responder atrasentan
    Reporting group description
    		 Participants who achieved < 30% reduction in their urinary albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive atrasentan in the Double-Blind Treatment Period

    Reporting group title
    Intent-to-Treat (ITT) Non-responder placebo
    Reporting group description
    		 Participants who achieved < 30% reduction in their urinary albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive placebo in the Double-Blind Treatment Period

    Reporting group values
    		 Intent-to-Treat (ITT) Responder atrasentan Intent-to-Treat (ITT) Responder placebo Intent-to-Treat (ITT) Non-responder atrasentan Intent-to-Treat (ITT) Non-responder placebo Total
    Number of subjects
    		 1325 1323 509 511 3668
    Age categorical
    Units: Subjects
    Age continuous
    Intent-to-Treat (ITT) Responders (participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period [EP]) and ITT Non-responders (Participants who achieved < 30% reduction in their UACR in the EP)
    Units: years
        arithmetic mean (standard deviation)
    		 64.9 ( 8.64 ) 64.7 ( 8.66 ) 63.8 ( 9.12 ) 63.6 ( 8.93 ) -
    Gender categorical
    Intent-to-Treat (ITT) Responders (participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period [EP]) and ITT Non-responders (Participants who achieved < 30% reduction in their UACR in the EP)
    Units: Subjects
        Female
    		 331 352 127 136 946
        Male
    		 994 971 382 375 2722

    End points

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    End points reporting groups
    Reporting group title
    Intent-to-Treat (ITT) Responder atrasentan
    Reporting group description
    		 Participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive atrasentan in the Double-Blind Treatment Period

    Reporting group title
    Intent-to-Treat (ITT) Responder placebo
    Reporting group description
    		 Participants who achieved at least 30% reduction in their albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive placebo in the Double-Blind Treatment Period

    Reporting group title
    Intent-to-Treat (ITT) Non-responder atrasentan
    Reporting group description
    		 Participants who achieved < 30% reduction in their urinary albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive atrasentan in the Double-Blind Treatment Period

    Reporting group title
    Intent-to-Treat (ITT) Non-responder placebo
    Reporting group description
    		 Participants who achieved < 30% reduction in their urinary albumin to creatinine ratio (UACR) in the Enrichment Period and were randomized to receive placebo in the Double-Blind Treatment Period

    Subject analysis set title
    Intent-to-Treat (ITT) Atrasentan
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized participants who entered the Double-Blind Treatment Period and were randomized to receive atrasentan

    Subject analysis set title
    Intent-to-Treat Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized participants who entered the Double-Blind Treatment Period and were randomized to receive placebo

    Primary: Time to the first occurrence of a component of the composite renal endpoint in the Intent-to-Treat (ITT) Responder Set (as randomized)

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    End point title
    		 Time to the first occurrence of a component of the composite renal endpoint in the Intent-to-Treat (ITT) Responder Set (as randomized) [1]
    End point description
    Time to the first occurrence of a component of the composite renal endpoint was defined as doubling of serum creatinine (confirmed by a 30-day serum creatinine measurement) or the onset of end stage renal disease (estimated glomerular filtration rate [eGFR] less than 15 ml/min/1.73 m^2 confirmed by a 90-day eGFR measurement, receiving chronic dialysis, renal transplantation, or renal death). Only events adjudicated by the Events Adjudication Committee (EAC) were considered in defining this endpoint. Data are presented as number of participants with a primary renal composite event (first event per participant). Analysis population: Intent-to-Treat (ITT) Responders (participants who achieved at least 30% reduction in their albumin to creatinine ratio [UACR] in the Enrichment Period [EP])
    End point type
    Primary
    End point timeframe
    From randomization to individual end of observation, up to 53 months
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The Intent-to-Treat Responder Set (as randomized) is the primary analysis for this endpoint.
    End point values
    		 Intent-to-Treat (ITT) Responder atrasentan Intent-to-Treat (ITT) Responder placebo
    Number of subjects analysed
    1325
    1323
    Units: Number of participants
    79
    105
    Statistical analysis title
    		 Stratified log-rank test
    Statistical analysis description
    The endpoint was analyzed using the stratified log-rank test for treatment comparison.
    Comparison groups
    Intent-to-Treat (ITT) Responder atrasentan v Intent-to-Treat (ITT) Responder placebo
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.029
    Method
    		 Stratified log-rank test
    Confidence interval
    Statistical analysis title
    		 Cox Proportional Hazard Ratio
    Statistical analysis description
    A Cox Proportional Hazards regression model with pre-specified covariates adjusted was used to estimate the hazard ratio of atrasentan to placebo and its 95% confidence interval.
    Comparison groups
    Intent-to-Treat (ITT) Responder atrasentan v Intent-to-Treat (ITT) Responder placebo
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.654
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.488
         upper limit
    		 0.878

    Secondary: Time to First Occurrence of a Component of Composite Renal Endpoint for All Randomized Participants (Pooled)

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    End point title
    		 Time to First Occurrence of a Component of Composite Renal Endpoint for All Randomized Participants (Pooled)
    End point description
    Time to the first occurrence of a component of the composite renal endpoint was defined as doubling of serum creatinine (confirmed by a 30-day serum creatinine measurement) or the onset of end stage renal disease (estimated glomerular filtration rate [eGFR] less than 15 ml/min/1.73 m^2 confirmed by a 90-day eGFR measurement, receiving chronic dialysis, renal transplantation, or renal death). Data for all randomized participants were pooled by treatment and analyzed. Data are presented as number of participants with a renal composite event (first event per participant). Analysis Population: Intent-to-treat population: participants who were randomized to receive either atrasentan or placebo during the Double-Blind Treatment Period
    End point type
    Secondary
    End point timeframe
    From randomization to individual end of observation, up to 53 months
    End point values
    		 Intent-to-Treat (ITT) Atrasentan Intent-to-Treat Placebo
    Number of subjects analysed
    1834
    1834
    Units: Number of participants
    152
    192
    Statistical analysis title
    		 Cox Proportional Hazard Ratio
    Statistical analysis description
    A Cox Proportional Hazards regression model with pre-specified covariates adjusted was used to estimate the hazard ratio of atrasentan to placebo and its 95% confidence interval.
    Comparison groups
    Intent-to-Treat Placebo v Intent-to-Treat (ITT) Atrasentan
    Number of subjects included in analysis
    3668
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.002
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.89

    Secondary: Time to Cardio-renal Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as randomized)

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    End point title
    		 Time to Cardio-renal Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as randomized) [2]
    End point description
    The composite event of interest for this outcome consisted of doubling of serum creatinine, end-stage renal disease (ESRD), cardiovascular (CV) death (including CV death and presumed CV death), nonfatal myocardial infarction (MI; heart attack) and nonfatal stroke. Presumed sudden cardiac death was included as a subcategory of presumed CV death. Only events adjudicated by the Events Adjudication Committee (EAC) were considered in defining this endpoint. Data are presented as number of participants with a cardio-renal composite event (first event per participant). Analysis Population: Intent-to-Treat (ITT) Responders (participants who achieved at least 30% reduction in their albumin to creatinine ratio [UACR] in the Enrichment Period [EP])
    End point type
    Secondary
    End point timeframe
    From randomization to individual end of observation, up to 53 months
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The Intent-to-Treat Responder Set (as randomized) is the primary analysis for this endpoint.
    End point values
    		 Intent-to-Treat (ITT) Responder atrasentan Intent-to-Treat (ITT) Responder placebo
    Number of subjects analysed
    1325
    1323
    Units: Number of participants
    147
    172
    Statistical analysis title
    		 Stratified log-rank test
    Statistical analysis description
    The endpoint was analyzed using the stratified log-rank test for treatment comparison.
    Comparison groups
    Intent-to-Treat (ITT) Responder atrasentan v Intent-to-Treat (ITT) Responder placebo
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.089
    Method
    		 Stratified log-rank test
    Confidence interval
    Statistical analysis title
    		 Cox Proportional Hazard Ratio
    Statistical analysis description
    A Cox Proportional Hazards regression model with pre-specified covariates adjusted was used to estimate the hazard ratio of atrasentan to placebo and its 95% confidence interval.
    Comparison groups
    Intent-to-Treat (ITT) Responder atrasentan v Intent-to-Treat (ITT) Responder placebo
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.049
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.801
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.642
         upper limit
    		 0.999

    Secondary: Time to a 50% Estimated Glomerular Filtration Rate Reduction in the Intent-to-Treat (ITT) Responder Set (as randomized)

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    End point title
    		 Time to a 50% Estimated Glomerular Filtration Rate Reduction in the Intent-to-Treat (ITT) Responder Set (as randomized) [3]
    End point description
    The event of interest for this outcome was a 50% reduction in a participant's estimated glomerular filtration rate (eGFR) value as compared to baseline, confirmed by a repeated value at least 20 days apart. The event time was defined as the first time that a 50% reduction in eGFR was observed. Data are presented as number of participants with a 50% reduction in eGFR (first event per participant). Analysis Population Description Intent-to-Treat (ITT) Responders (participants who achieved at least 30% reduction in their albumin to creatinine ratio [UACR] in the Enrichment Period [EP])
    End point type
    Secondary
    End point timeframe
    From randomization to individual end of observation, up to 53 months
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The Intent-to-Treat Responder Set (as randomized) is the primary analysis for this endpoint.
    End point values
    		 Intent-to-Treat (ITT) Responder atrasentan Intent-to-Treat (ITT) Responder placebo
    Number of subjects analysed
    1325
    1323
    Units: Number of participants
    78
    88
    Statistical analysis title
    		 Stratified log-rank test
    Statistical analysis description
    The endpoint was analyzed using the stratified log-rank test for treatment comparison.
    Comparison groups
    Intent-to-Treat (ITT) Responder atrasentan v Intent-to-Treat (ITT) Responder placebo
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.289
    Method
    		 Stratified log-rank test
    Confidence interval
    Statistical analysis title
    		 Cox Proportional Hazard Ratio
    Statistical analysis description
    A Cox Proportional Hazards regression model with pre-specified covariates adjusted was used to estimate the hazard ratio of atrasentan to placebo and its 95% confidence interval.
    Comparison groups
    Intent-to-Treat (ITT) Responder atrasentan v Intent-to-Treat (ITT) Responder placebo
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.112
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.779
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.573
         upper limit
    		 1.06

    Secondary: Time to the Cardiovascular Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as randomized)

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    End point title
    		 Time to the Cardiovascular Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as randomized) [4]
    End point description
    The composite event of interest for this outcome was cardiovascular (CV) death (CV death, presumed CV death), nonfatal myocardial infarction (MI; heart attack), and nonfatal stroke. Presumed sudden cardiac death was included as a sub-category of presumed CV death. Only events adjudicated by the Events Adjudication Committee (EAC) were used. Data are presented as number of participants with a cardiovascular composite event (first event per participant).
    End point type
    Secondary
    End point timeframe
    From randomization to individual end of observation, up to 53 months
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The Intent-to-Treat Responder Set (as randomized) is the primary analysis for this endpoint.
    End point values
    		 Intent-to-Treat (ITT) Responder atrasentan Intent-to-Treat (ITT) Responder placebo
    Number of subjects analysed
    1325
    1323
    Units: Number of participants
    72
    81
    Statistical analysis title
    		 Stratified log-rank test
    Statistical analysis description
    The endpoint was analyzed using the stratified log-rank test for treatment comparison.
    Comparison groups
    Intent-to-Treat (ITT) Responder atrasentan v Intent-to-Treat (ITT) Responder placebo
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.446
    Method
    		 Stratified log-rank test
    Confidence interval
    Statistical analysis title
    		 Cox Proportional Hazard Ratio
    Statistical analysis description
    A Cox Proportional Hazards regression model with pre-specified covariates adjusted was used to estimate the hazard ratio of atrasentan to placebo and its 95% confidence interval.
    Comparison groups
    Intent-to-Treat (ITT) Responder placebo v Intent-to-Treat (ITT) Responder atrasentan
    Number of subjects included in analysis
    2648
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.447
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.884
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.643
         upper limit
    		 1.215

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) reported from time of study drug administration until 45 d after last dose (up to 24 wks for All Atrasentan Set in EP; 54 mos for ITT sets in Double-Blind period)
    Adverse event reporting additional description
    TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 45 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    All Atrasentan Set
    Reporting group description
    		 Participants who received at least one dose of atrasentan, including both Enrichment and Double-Blind Treatment Periods

    Reporting group title
    Double-Blind Placebo
    Reporting group description
    		 All participants who received at least one dose of placebo during the Double-Blind Treatment Period

    Reporting group title
    Double-Blind Atrasentan
    Reporting group description
    		 All participants who received at least one dose of atrasentan during the Double-Blind Treatment Period

    Serious adverse events
    		 All Atrasentan Set Double-Blind Placebo Double-Blind Atrasentan
    Total subjects affected by serious adverse events
         subjects affected / exposed
    292 / 5107 (5.72%)
    626 / 1830 (34.21%)
    685 / 1829 (37.45%)
         number of deaths (all causes)
    25
    79
    84
         number of deaths resulting from adverse events
    23
    64
    65
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ACUTE MYELOID LEUKAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    ADENOCARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ADENOCARCINOMA GASTRIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ADENOCARCINOMA OF COLON
         subjects affected / exposed
    2 / 5107 (0.04%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ADENOCARCINOMA PANCREAS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ADRENAL NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATYPICAL FIBROXANTHOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BENIGN NEOPLASM OF BLADDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BASAL CELL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BENIGN RENAL NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BENIGN NEOPLASM OF THYROID GLAND
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLADDER CANCER
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BILE DUCT CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLADDER CANCER STAGE I, WITH CANCER IN SITU
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLADDER CANCER RECURRENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLADDER NEOPLASM
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLADDER TRANSITIONAL CELL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRAIN NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    BONE NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRAIN NEOPLASM BENIGN
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BREAST CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BREAST NEOPLASM
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BREAST CANCER RECURRENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARCINOID TUMOUR PULMONARY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRONCHIAL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC LYMPHOCYTIC LEUKAEMIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLANGIOCARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    COLON CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLON ADENOMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLORECTAL CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLON NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIFFUSE LARGE B-CELL LYMPHOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENDOMETRIAL CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GALLBLADDER CANCER METASTATIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    GASTRIC ADENOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    6 / 1830 (0.33%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL TRACT ADENOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GLIOBLASTOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    HEPATOCELLULAR CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HUERTHLE CELL CARCINOMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFLAMMATORY PSEUDOTUMOUR
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL ADENOCARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTRADUCTAL PROLIFERATIVE BREAST LESION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LANGERHANS CELL SARCOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARYNGEAL SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIPOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIPOSARCOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUNG ADENOCARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUNG ADENOCARCINOMA STAGE IV
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    LUNG CANCER METASTATIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    LUNG NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUNG NEOPLASM MALIGNANT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LYMPHOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MALIGNANT PALATE NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METASTATIC CARCINOMA OF THE BLADDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    METASTATIC MALIGNANT MELANOMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METASTATIC NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUCINOUS ADENOCARCINOMA OF APPENDIX
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NASOPHARYNGEAL CANCER
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUROENDOCRINE CARCINOMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUROENDOCRINE TUMOUR OF THE LUNG
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    OROPHARYNGEAL NEOPLASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOSARCOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    OVARIAN ADENOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OVARIAN CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    PANCREATIC CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATIC CARCINOMA METASTATIC
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    PITUITARY TUMOUR BENIGN
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROSTATE CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    7 / 1830 (0.38%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PLASMA CELL MYELOMA
         subjects affected / exposed
    2 / 5107 (0.04%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    PROSTATE CANCER RECURRENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PSEUDOMYXOMA PERITONEI
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROSTATIC ADENOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL CANCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RECTAL ADENOCARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL CELL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL CANCER METASTATIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SINONASAL PAPILLOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL ONCOCYTOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SMALL CELL LUNG CANCER METASTATIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF LUNG
         subjects affected / exposed
    2 / 5107 (0.04%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF THE HYPOPHARYNX
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    SQUAMOUS CELL CARCINOMA OF THE ORAL CAVITY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSITIONAL CELL CARCINOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THYROID NEOPLASM
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSITIONAL CELL CARCINOMA RECURRENT
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UTERINE LEIOMYOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    ANEURYSM
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    AORTIC ANEURYSM
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    AORTIC STENOSIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    AORTIC ANEURYSM RUPTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    ARTERIOSCLEROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    ARTERIAL STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTERIAL DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD PRESSURE INADEQUATELY CONTROLLED
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTERITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC VASCULAR DISORDER
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    4 / 1830 (0.22%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DRY GANGRENE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EXTREMITY NECROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    9 / 1830 (0.49%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 9
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSIVE CRISIS
         subjects affected / exposed
    2 / 5107 (0.04%)
    4 / 1830 (0.22%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSIVE EMERGENCY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOVOLAEMIC SHOCK
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    4 / 5107 (0.08%)
    4 / 1830 (0.22%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    4 / 5
    1 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
         subjects affected / exposed
    1 / 5107 (0.02%)
    7 / 1830 (0.38%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 10
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MALIGNANT HYPERTENSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERY STENOSIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERY OCCLUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERY THROMBOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL VASCULAR DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ISCHAEMIA
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SHOCK HAEMORRHAGIC
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    PERIPHERAL VENOUS DISEASE
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBCLAVIAN ARTERY OCCLUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THROMBOPHLEBITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VASCULAR OCCLUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    BRAIN DEATH
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    ASTHENIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHEST DISCOMFORT
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    1 / 5107 (0.02%)
    4 / 1830 (0.22%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHILLS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    3 / 5107 (0.06%)
    4 / 1830 (0.22%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    2 / 3
    0 / 4
    1 / 5
    DISEASE COMPLICATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FACE OEDEMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEELING ABNORMAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GENERALISED OEDEMA
         subjects affected / exposed
    2 / 5107 (0.04%)
    3 / 1830 (0.16%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOTHERMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IMPAIRED HEALING
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MULTIPLE ORGAN DYSFUNCTION SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 4
    NECROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    4 / 5107 (0.08%)
    3 / 1830 (0.16%)
    6 / 1829 (0.33%)
         occurrences causally related to treatment / all
    3 / 4
    3 / 3
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL SWELLING
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUDDEN CARDIAC DEATH
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    SUDDEN DEATH
         subjects affected / exposed
    1 / 5107 (0.02%)
    5 / 1830 (0.27%)
    8 / 1829 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 5
    1 / 8
         deaths causally related to treatment / all
    0 / 1
    2 / 5
    1 / 8
    SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VASCULAR STENT STENOSIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    ALLERGY TO ARTHROPOD BITE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAPHYLACTIC SHOCK
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERSENSITIVITY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    OVERWORK
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    BENIGN PROSTATIC HYPERPLASIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    7 / 1830 (0.38%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EPIDIDYMAL CYST
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GYNAECOMASTIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROSTATITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SCROTAL OEDEMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UTERINE PROLAPSE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE PULMONARY OEDEMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    6 / 1830 (0.33%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 6
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    1 / 2
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    9 / 1830 (0.49%)
    11 / 1829 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 9
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASPIRATION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    ASTHMA
         subjects affected / exposed
    3 / 5107 (0.06%)
    3 / 1830 (0.16%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    BRONCHOSPASM
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    3 / 5107 (0.06%)
    6 / 1830 (0.33%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COUGH
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EPISTAXIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOTHORAX
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYDROTHORAX
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERCAPNIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOVENTILATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOXIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MEDIASTINAL CYST
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OBSTRUCTIVE AIRWAYS DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMOMEDIASTINUM
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    6 / 1829 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY CONGESTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    PULMONARY HYPERTENSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY MASS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY OEDEMA
         subjects affected / exposed
    6 / 5107 (0.12%)
    4 / 1830 (0.22%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 5
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY ARREST
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    RESPIRATORY DISTRESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    3 / 5107 (0.06%)
    8 / 1830 (0.44%)
    6 / 1829 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    1 / 4
    0 / 1
    RESTRICTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SLEEP APNOEA SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    AGITATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANXIETY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BIPOLAR DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DELIRIUM
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DELUSIONAL DISORDER, SOMATIC TYPE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DISORIENTATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEPRESSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DRUG ABUSE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INSOMNIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENTAL STATUS CHANGES
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MAJOR DEPRESSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUICIDAL IDEATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device capturing issue
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    BILE DUCT STONE
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BILIARY COLIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLANGITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    6 / 1829 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS CHRONIC
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DRUG-INDUCED LIVER INJURY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GALLBLADDER PERFORATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC CIRRHOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC LESION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC STEATOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS ACUTE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD BICARBONATE DECREASED
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    1 / 5107 (0.02%)
    7 / 1830 (0.38%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD GLUCOSE DECREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD POTASSIUM INCREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD UREA INCREASED
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRAIN NATRIURETIC PEPTIDE INCREASED
         subjects affected / exposed
    2 / 5107 (0.04%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ELECTROCARDIOGRAM Q WAVE ABNORMAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GLOMERULAR FILTRATION RATE DECREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOGLOBIN DECREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HELICOBACTER TEST POSITIVE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC ENZYME INCREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTRAOCULAR PRESSURE INCREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIPASE INCREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROSTATIC SPECIFIC ANTIGEN INCREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROTEIN URINE PRESENT
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TROPONIN INCREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINE CYTOLOGY ABNORMAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WEIGHT INCREASED
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ABDOMINAL INJURY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANKLE FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL WOUND DEHISCENCE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRAIN CONTUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLADDER INJURY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BURNS SECOND DEGREE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CERVICAL VERTEBRAL FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLAVICLE FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONCUSSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONTUSION
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS RADIATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CRANIOCEREBRAL INJURY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FACIAL BONES FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DISLOCATION OF VERTEBRA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    7 / 5107 (0.14%)
    5 / 1830 (0.27%)
    12 / 1829 (0.66%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEMORAL NECK FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FIBULA FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FOOT FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FOREIGN BODY IN GASTROINTESTINAL TRACT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GRAFT THROMBOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAND FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEAD INJURY
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ILIUM FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INCISIONAL HERNIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INJURY
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JAW FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JOINT DISLOCATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LACERATION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIGAMENT SPRAIN
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIMB INJURY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIMB TRAUMATIC AMPUTATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LISFRANC FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOWER LIMB FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUMBAR VERTEBRAL FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    4 / 1830 (0.22%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENISCUS INJURY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MULTIPLE FRACTURES
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCLE RUPTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OVERDOSE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATIC LEAK
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PATELLA FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PELVIC FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST CONCUSSION SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL DISCHARGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL HAEMATOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL HAEMORRHAGE
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    POST PROCEDURAL SWELLING
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND COMPLICATION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL PAIN
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PUBIS FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RADIUS FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RIB FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SKIN ABRASION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    SPINAL FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL CORD INJURY CERVICAL
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBARACHNOID HAEMORRHAGE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBDURAL HAEMATOMA
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBDURAL HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THORACIC VERTEBRAL FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TENDON RUPTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THERMAL BURN
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TOXICITY TO VARIOUS AGENTS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TIBIA FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRAUMATIC HAEMATOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRAUMATIC FRACTURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRAUMATIC LUNG INJURY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRAUMATIC HAEMOTHORAX
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ULNA FRACTURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ULNAR NERVE INJURY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VASCULAR PSEUDOANEURYSM
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY RETENTION POSTOPERATIVE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND COMPLICATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND DEHISCENCE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND NECROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE CORONARY SYNDROME
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACUTE LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    7 / 5107 (0.14%)
    28 / 1830 (1.53%)
    34 / 1829 (1.86%)
         occurrences causally related to treatment / all
    1 / 7
    1 / 29
    4 / 40
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    0 / 2
    ADAMS-STOKES SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANGINA PECTORIS
         subjects affected / exposed
    4 / 5107 (0.08%)
    10 / 1830 (0.55%)
    10 / 1829 (0.55%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 10
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANGINA UNSTABLE
         subjects affected / exposed
    4 / 5107 (0.08%)
    3 / 1830 (0.16%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    AORTIC VALVE STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARRHYTHMIA SUPRAVENTRICULAR
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARRHYTHMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    ARTERIOSCLEROSIS CORONARY ARTERY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    ATRIAL FIBRILLATION
         subjects affected / exposed
    2 / 5107 (0.04%)
    10 / 1830 (0.55%)
    16 / 1829 (0.87%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 11
    4 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FLUTTER
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL TACHYCARDIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK COMPLETE
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK FIRST DEGREE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK SECOND DEGREE
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRADYARRHYTHMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRADYCARDIA
         subjects affected / exposed
    3 / 5107 (0.06%)
    2 / 1830 (0.11%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BUNDLE BRANCH BLOCK BILATERAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BUNDLE BRANCH BLOCK RIGHT
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BUNDLE BRANCH BLOCK LEFT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    3 / 5107 (0.06%)
    5 / 1830 (0.27%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 5
    1 / 4
         deaths causally related to treatment / all
    1 / 3
    1 / 5
    1 / 3
    CARDIAC FAILURE
         subjects affected / exposed
    5 / 5107 (0.10%)
    11 / 1830 (0.60%)
    19 / 1829 (1.04%)
         occurrences causally related to treatment / all
    4 / 5
    5 / 11
    6 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    CARDIAC FAILURE ACUTE
         subjects affected / exposed
    4 / 5107 (0.08%)
    4 / 1830 (0.22%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 5
    4 / 6
         deaths causally related to treatment / all
    1 / 2
    0 / 1
    1 / 1
    CARDIAC FAILURE CHRONIC
         subjects affected / exposed
    3 / 5107 (0.06%)
    2 / 1830 (0.11%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 2
    1 / 5
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    22 / 5107 (0.43%)
    22 / 1830 (1.20%)
    37 / 1829 (2.02%)
         occurrences causally related to treatment / all
    17 / 22
    7 / 23
    15 / 41
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    CARDIO-RESPIRATORY ARREST
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    0 / 3
    CARDIOGENIC SHOCK
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    CARDIOMYOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    CARDIOPULMONARY FAILURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    CARDIORENAL SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARDIOVASCULAR DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    6 / 5107 (0.12%)
    19 / 1830 (1.04%)
    29 / 1829 (1.59%)
         occurrences causally related to treatment / all
    1 / 6
    1 / 20
    3 / 31
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    CORONARY ARTERY OCCLUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CORONARY ARTERY STENOSIS
         subjects affected / exposed
    3 / 5107 (0.06%)
    2 / 1830 (0.11%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CORONARY ARTERY THROMBOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    CYANOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIASTOLIC DYSFUNCTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSIVE CARDIOMYOPATHY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSIVE HEART DISEASE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    ISCHAEMIC CARDIOMYOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    3 / 5107 (0.06%)
    1 / 1830 (0.05%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MITRAL VALVE INCOMPETENCE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    7 / 5107 (0.14%)
    8 / 1830 (0.44%)
    13 / 1829 (0.71%)
         occurrences causally related to treatment / all
    3 / 7
    0 / 8
    4 / 15
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    MYOCARDIAL ISCHAEMIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    4 / 1830 (0.22%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PALPITATIONS
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    SINOATRIAL BLOCK
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SINUS ARREST
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SINUS NODE DYSFUNCTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    2 / 5107 (0.04%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TACHYCARDIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENTRICULAR EXTRASYSTOLES
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENTRICULAR FIBRILLATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    VENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    ACUTE MOTOR AXONAL NEUROPATHY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ALTERED STATE OF CONSCIOUSNESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    APHASIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BALANCE DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRAIN STEM INFARCTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CAROTID ARTERY OCCLUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CAROTID ARTERY STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARPAL TUNNEL SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBELLAR HAEMATOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBELLAR INFARCTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    CEREBRAL INFARCTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    8 / 1830 (0.44%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 9
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    CEREBRAL ISCHAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL THROMBOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    5 / 5107 (0.10%)
    14 / 1830 (0.77%)
    13 / 1829 (0.71%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 14
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    CEREBROVASCULAR DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CERVICOBRACHIAL SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    DEMENTIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC COMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC HYPERGLYCAEMIC COMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC HYPEROSMOLAR COMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC NEUROPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIZZINESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMBOLIC CEREBRAL INFARCTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENCEPHALOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FACIAL PARALYSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGIC STROKE
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    HEMIPARESIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYDROCEPHALUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSIVE ENCEPHALOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOGLYCAEMIC SEIZURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    3 / 5107 (0.06%)
    9 / 1830 (0.49%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 10
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    ISCHAEMIC CEREBRAL INFARCTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IVTH NERVE PARALYSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LACUNAR INFARCTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOSS OF CONSCIOUSNESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUMBAR RADICULOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METABOLIC ENCEPHALOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MIGRAINE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MONONEUROPATHY MULTIPLEX
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYELOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOCLONUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PARAESTHESIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    QUADRIPLEGIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PRESYNCOPE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RADICULOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SCIATICA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SENILE DEMENTIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL CORD DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPONDYLITIC MYELOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STATUS EPILEPTICUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYNCOPE
         subjects affected / exposed
    3 / 5107 (0.06%)
    11 / 1830 (0.60%)
    6 / 1829 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 11
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THALAMIC INFARCTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    2 / 5107 (0.04%)
    7 / 1830 (0.38%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VASCULAR DEMENTIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    7 / 5107 (0.14%)
    11 / 1830 (0.60%)
    27 / 1829 (1.48%)
         occurrences causally related to treatment / all
    2 / 7
    1 / 15
    3 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAEMIA OF CHRONIC DISEASE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    AUTOIMMUNE HAEMOLYTIC ANAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COAGULOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DISSEMINATED INTRAVASCULAR COAGULATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGIC ANAEMIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IRON DEFICIENCY ANAEMIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEUKOCYTOSIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MICROCYTIC ANAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEPHROGENIC ANAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    MENIERE'S DISEASE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VERTIGO
         subjects affected / exposed
    1 / 5107 (0.02%)
    7 / 1830 (0.38%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VERTIGO POSITIONAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    AGE-RELATED MACULAR DEGENERATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANGLE CLOSURE GLAUCOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLINDNESS TRANSIENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATARACT
         subjects affected / exposed
    3 / 5107 (0.06%)
    10 / 1830 (0.55%)
    19 / 1829 (1.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 12
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATARACT DIABETIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATARACT NUCLEAR
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CORNEAL EPITHELIUM DEFECT
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CORNEAL OPACITY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DACRYOSTENOSIS ACQUIRED
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC RETINOPATHY
         subjects affected / exposed
    2 / 5107 (0.04%)
    0 / 1830 (0.00%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIPLOPIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EYE HAEMORRHAGE
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EYELID PTOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GLAUCOMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LAGOPHTHALMOS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MACULAR FIBROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MACULAR OEDEMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OPTIC ISCHAEMIC NEUROPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIORBITAL OEDEMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RETINAL DETACHMENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RETINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RETINOPATHY PROLIFERATIVE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RHEGMATOGENOUS RETINAL DETACHMENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRACTIONAL RETINAL DETACHMENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VISUAL IMPAIRMENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VITREOUS ADHESIONS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VITREOUS HAEMORRHAGE
         subjects affected / exposed
    4 / 5107 (0.08%)
    5 / 1830 (0.27%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL HERNIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAL INCONTINENCE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANORECTAL ULCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASCITES
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC GASTRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLITIS ULCERATIVE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DENTAL CARIES
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC GASTROPARESIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC GASTROPATHY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULUM
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULUM INTESTINAL HAEMORRHAGIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DUODENAL ULCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DUODENAL ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DUODENITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPHAGIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROVESICAL FISTULA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EROSIVE DUODENITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC FISTULA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC MUCOSAL HYPERTROPHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC POLYPS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC ULCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC ULCER HAEMORRHAGE
         subjects affected / exposed
    2 / 5107 (0.04%)
    3 / 1830 (0.16%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS HAEMORRHAGIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    6 / 1829 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL MUCOSAL DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HIATUS HERNIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ILEUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IMPAIRED GASTRIC EMPTYING
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INGUINAL HERNIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL PERFORATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IRRITABLE BOWEL SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE POLYP
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOWER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LYMPHOCYTIC OESOPHAGITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MELAENA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    2 / 5107 (0.04%)
    1 / 1830 (0.05%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OBSTRUCTIVE PANCREATITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    OESOPHAGEAL SPASM
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL ULCER HAEMORRHAGE
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATIC DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    2 / 5107 (0.04%)
    4 / 1830 (0.22%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    1 / 5107 (0.02%)
    4 / 1830 (0.22%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PEPTIC ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PEPTIC ULCER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROCTITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RECTAL ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RECTAL POLYP
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UMBILICAL HERNIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ULCERATIVE GASTRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    3 / 5107 (0.06%)
    5 / 1830 (0.27%)
    7 / 1829 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    ACTINIC KERATOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANGIOEDEMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC CHEIROARTHROPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DECUBITUS ULCER
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC FOOT
         subjects affected / exposed
    1 / 5107 (0.02%)
    10 / 1830 (0.55%)
    8 / 1829 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 10
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ECZEMA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INGROWING NAIL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PRURITUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SKIN DISCOLOURATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SKIN ULCER
         subjects affected / exposed
    4 / 5107 (0.08%)
    3 / 1830 (0.16%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    19 / 5107 (0.37%)
    36 / 1830 (1.97%)
    54 / 1829 (2.95%)
         occurrences causally related to treatment / all
    3 / 20
    7 / 40
    4 / 56
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    AZOTAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    BLADDER STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CALCULUS URINARY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC KIDNEY DISEASE
         subjects affected / exposed
    1 / 5107 (0.02%)
    13 / 1830 (0.71%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 13
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC NEPHROPATHY
         subjects affected / exposed
    2 / 5107 (0.04%)
    10 / 1830 (0.55%)
    17 / 1829 (0.93%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 11
    1 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    END STAGE RENAL DISEASE
         subjects affected / exposed
    0 / 5107 (0.00%)
    27 / 1830 (1.48%)
    19 / 1829 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 30
    1 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GLOMERULONEPHRITIS MEMBRANOUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGE URINARY TRACT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYDRONEPHROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYDROURETER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEPHROPATHY TOXIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROTEINURIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL ARTERY STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    2 / 5107 (0.04%)
    5 / 1830 (0.27%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    RENAL IMPAIRMENT
         subjects affected / exposed
    3 / 5107 (0.06%)
    13 / 1830 (0.71%)
    10 / 1829 (0.55%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 14
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL VASCULITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URETERIC OBSTRUCTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URETEROLITHIASIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URETHRAL STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY BLADDER POLYP
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT OBSTRUCTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    GOITRE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERPARATHYROIDISM PRIMARY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTHRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTHROPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    0 / 5107 (0.00%)
    4 / 1830 (0.22%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CERVICAL SPINAL STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COSTOCHONDRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COMPARTMENT SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMARTHROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GOUTY ARTHRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    4 / 1830 (0.22%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC DISORDER
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC DEGENERATION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC PROTRUSION
         subjects affected / exposed
    0 / 5107 (0.00%)
    4 / 1830 (0.22%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC DISPLACEMENT
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JOINT SWELLING
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUMBAR SPINAL STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENISCAL DEGENERATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MOBILITY DECREASED
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYALGIA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 5107 (0.00%)
    5 / 1830 (0.27%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NECK PAIN
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUROPATHIC ARTHROPATHY
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOARTHRITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    16 / 1830 (0.87%)
    8 / 1829 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 19
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOPOROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POLYARTHRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RHABDOMYOLYSIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ROTATOR CUFF SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SACROILIITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SOFT TISSUE NECROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL COLUMN STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL INSTABILITY
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL LIGAMENT OSSIFICATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL OSTEOARTHRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPONDYLITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPONDYLOLISTHESIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYMPATHETIC POSTERIOR CERVICAL SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYNOVIAL CYST
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYNOVITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THORACIC SPINAL STENOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TORTICOLLIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABSCESS LIMB
         subjects affected / exposed
    0 / 5107 (0.00%)
    6 / 1830 (0.33%)
    6 / 1829 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABSCESS SOFT TISSUE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACUTE SINUSITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAL ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    2 / 5107 (0.04%)
    3 / 1830 (0.16%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTERIOSCLEROTIC GANGRENE
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTHRITIS BACTERIAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTHRITIS INFECTIVE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACTERAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACTERIAL DIARRHOEA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACTERIAL SEPSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BILIARY SEPSIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRAIN ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    4 / 1830 (0.22%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS BACTERIAL
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CAMPYLOBACTER GASTROENTERITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CAMPYLOBACTER INFECTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    5 / 5107 (0.10%)
    22 / 1830 (1.20%)
    14 / 1829 (0.77%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 24
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS GANGRENOUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS INFECTIVE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIAL SEPSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC TONSILLITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS KLEBSIELLA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DENGUE FEVER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC FOOT INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    4 / 1830 (0.22%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC GANGRENE
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMPHYSEMATOUS PYELONEPHRITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENDOCARDITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENDOPHTHALMITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTERITIS INFECTIOUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROBACTER INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ERYSIPELAS
         subjects affected / exposed
    1 / 5107 (0.02%)
    3 / 1830 (0.16%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOCCAL INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA BACTERAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA SEPSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    ESCHERICHIA URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GANGRENE
         subjects affected / exposed
    1 / 5107 (0.02%)
    7 / 1830 (0.38%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GAS GANGRENE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    10 / 1830 (0.55%)
    8 / 1829 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 10
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GRAFT INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HELICOBACTER INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS B
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS C
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTED SKIN ULCER
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTIVE EXACERBATION OF BRONCHIECTASIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    2 / 5107 (0.04%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISCITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JOINT ABSCESS
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    KLEBSIELLA INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEPTOSPIROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIVER ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOCALISED INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    2 / 5107 (0.04%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MASTOIDITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MEDICAL DEVICE SITE INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MORGANELLA INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NECROTISING FASCIITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NOSOCOMIAL INFECTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ORCHITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOMYELITIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    10 / 1830 (0.55%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 11
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOMYELITIS ACUTE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOMYELITIS CHRONIC
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OTITIS EXTERNA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OTITIS MEDIA ACUTE
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OTITIS MEDIA CHRONIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS BACTERIAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAROTID ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIODONTITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIRECTAL ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERITONITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    PERITONSILLAR ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PHARYNGEAL ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PILONIDAL CYST
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    14 / 5107 (0.27%)
    41 / 1830 (2.24%)
    54 / 1829 (2.95%)
         occurrences causally related to treatment / all
    0 / 14
    3 / 43
    2 / 63
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    4 / 1829 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA LEGIONELLA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA PARAINFLUENZAE VIRAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA PSEUDOMONAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA STAPHYLOCOCCAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA STREPTOCOCCAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA VIRAL
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL CELLULITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND INFECTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROSTATIC ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROSTATITIS ESCHERICHIA COLI
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PSEUDOMONAS INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY TUBERCULOMA
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    3 / 5107 (0.06%)
    4 / 1830 (0.22%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS ACUTE
         subjects affected / exposed
    0 / 5107 (0.00%)
    4 / 1830 (0.22%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS CHRONIC
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RHINITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    4 / 5107 (0.08%)
    18 / 1830 (0.98%)
    16 / 1829 (0.87%)
         occurrences causally related to treatment / all
    0 / 4
    2 / 18
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
    SEPSIS SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPTIC EMBOLUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPTIC ENCEPHALOPATHY
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPTIC NECROSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    1 / 5107 (0.02%)
    6 / 1830 (0.33%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    SIALOADENITIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL BACTERAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL SEPSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STREPTOCOCCAL BACTERAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYSTEMIC CANDIDA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TOOTH ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TOXIC SHOCK SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TUBERCULOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    6 / 5107 (0.12%)
    12 / 1830 (0.66%)
    21 / 1829 (1.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 15
    1 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION ENTEROCOCCAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION BACTERIAL
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VULVAL ABSCESS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND INFECTION
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND SEPSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND INFECTION STAPHYLOCOCCAL
         subjects affected / exposed
    1 / 5107 (0.02%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    CACHEXIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DECREASED APPETITE
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    7 / 5107 (0.14%)
    8 / 1830 (0.44%)
    11 / 1829 (0.60%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETES MELLITUS
         subjects affected / exposed
    1 / 5107 (0.02%)
    4 / 1830 (0.22%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETES MELLITUS INADEQUATE CONTROL
         subjects affected / exposed
    3 / 5107 (0.06%)
    7 / 1830 (0.38%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC KETOACIDOSIS
         subjects affected / exposed
    1 / 5107 (0.02%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC KETOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC METABOLIC DECOMPENSATION
         subjects affected / exposed
    0 / 5107 (0.00%)
    3 / 1830 (0.16%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ELECTROLYTE IMBALANCE
         subjects affected / exposed
    0 / 5107 (0.00%)
    2 / 1830 (0.11%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FLUID OVERLOAD
         subjects affected / exposed
    2 / 5107 (0.04%)
    3 / 1830 (0.16%)
    9 / 1829 (0.49%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 3
    3 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FLUID RETENTION
         subjects affected / exposed
    2 / 5107 (0.04%)
    0 / 1830 (0.00%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GOUT
         subjects affected / exposed
    1 / 5107 (0.02%)
    2 / 1830 (0.11%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERCALCAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERGLYCAEMIA
         subjects affected / exposed
    2 / 5107 (0.04%)
    9 / 1830 (0.49%)
    8 / 1829 (0.44%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 11
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERGLYCAEMIC HYPEROSMOLAR NONKETOTIC SYNDROME
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERKALAEMIA
         subjects affected / exposed
    5 / 5107 (0.10%)
    16 / 1830 (0.87%)
    16 / 1829 (0.87%)
         occurrences causally related to treatment / all
    1 / 6
    3 / 19
    2 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERURICAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOMAGNESAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    2 / 5107 (0.04%)
    2 / 1830 (0.11%)
    3 / 1829 (0.16%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOGLYCAEMIA
         subjects affected / exposed
    13 / 5107 (0.25%)
    12 / 1830 (0.66%)
    22 / 1829 (1.20%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 14
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOVOLAEMIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOPHAGIA
         subjects affected / exposed
    0 / 5107 (0.00%)
    0 / 1830 (0.00%)
    1 / 1829 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METABOLIC ACIDOSIS
         subjects affected / exposed
    0 / 5107 (0.00%)
    6 / 1830 (0.33%)
    5 / 1829 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    OBESITY
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    2 / 1829 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TYPE 2 DIABETES MELLITUS
         subjects affected / exposed
    0 / 5107 (0.00%)
    1 / 1830 (0.05%)
    0 / 1829 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All Atrasentan Set Double-Blind Placebo Double-Blind Atrasentan
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1781 / 5107 (34.87%)
    1038 / 1830 (56.72%)
    1043 / 1829 (57.03%)
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    78 / 5107 (1.53%)
    218 / 1830 (11.91%)
    158 / 1829 (8.64%)
         occurrences all number
    79
    257
    179
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    180 / 5107 (3.52%)
    127 / 1830 (6.94%)
    216 / 1829 (11.81%)
         occurrences all number
    183
    138
    241
    General disorders and administration site conditions
    OEDEMA PERIPHERAL
         subjects affected / exposed
    1148 / 5107 (22.48%)
    483 / 1830 (26.39%)
    534 / 1829 (29.20%)
         occurrences all number
    1273
    666
    765
    Gastrointestinal disorders
    DIARRHOEA
         subjects affected / exposed
    103 / 5107 (2.02%)
    103 / 1830 (5.63%)
    99 / 1829 (5.41%)
         occurrences all number
    108
    110
    116
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    61 / 5107 (1.19%)
    125 / 1830 (6.83%)
    88 / 1829 (4.81%)
         occurrences all number
    62
    133
    93
    Infections and infestations
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    110 / 5107 (2.15%)
    114 / 1830 (6.23%)
    106 / 1829 (5.80%)
         occurrences all number
    114
    140
    131
    NASOPHARYNGITIS
         subjects affected / exposed
    145 / 5107 (2.84%)
    169 / 1830 (9.23%)
    180 / 1829 (9.84%)
         occurrences all number
    152
    278
    274
    URINARY TRACT INFECTION
         subjects affected / exposed
    50 / 5107 (0.98%)
    93 / 1830 (5.08%)
    93 / 1829 (5.08%)
         occurrences all number
    51
    135
    126
    Metabolism and nutrition disorders
    HYPERKALAEMIA
         subjects affected / exposed
    77 / 5107 (1.51%)
    143 / 1830 (7.81%)
    132 / 1829 (7.22%)
         occurrences all number
    77
    165
    159
    HYPERURICAEMIA
         subjects affected / exposed
    84 / 5107 (1.64%)
    105 / 1830 (5.74%)
    101 / 1829 (5.52%)
         occurrences all number
    85
    106
    105
    HYPOGLYCAEMIA
         subjects affected / exposed
    126 / 5107 (2.47%)
    120 / 1830 (6.56%)
    114 / 1829 (6.23%)
         occurrences all number
    189
    212
    193

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2014
    ● ESRD for primary endpoint: confirmed eGFR < 15 mL/min/1.73 m^2 ● Other endpoints: Changed time to 30% eGFR reduction after 2 mos post-random to 50% eGFR reduction; change from Baseline (BL) to 24 mo post-random on UACR new endpoint; made time to first occurrence of component of composite renal endpoint new endpoint; added endpoints about vascular events and laser photocoagulations ● Inclusion criterion (IC) 3: antihyperglycemic meds and ACE inhibitor or angiotensin receptor blocker at least 4 wks prior to screening visit 2; latent autoimmune diabetes or insulin-treated w/o history of diabetic ketoacidosis who also have a negative anti-GAD test + an elevated post-prandial serum C-peptide level ● IC 5: serum albumin criteria ≥ 2.5 g/dL (25 g/L); serum K upper limit =6.0 mEq/L; upper limit of systolic BP =180 mmHg; eligible BP at any time during screening ● IC 7: remove acute kidney injury; subjects may not have a weight gain ≥ 3 kg AND brain natriuretic peptide (BNP) ≥ 300 pg/mL last visit of the enrichment period compared to BL ● IC 8: dual contraception acceptable forms ● Removed HbA1c IC ● Exclusion criterion (EC) 1: removed moderate edema and pulmonary edema; updated time frame from 6 mos to 4 wks prior to screening. ● EC 2: subject has history of pulmonary hypertension, pulmonary fibrosis or any lung disease requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema) ● EC 15: include atrasentan use ● Removed EC for Hx of symptomatic hypotension, BMI, and pioglitazone ● Added EC 22: subjects considered to be clinically unstable regarding general, metabolic or CV health determined by investigator ● Removed UACR blind during Enrichment Period ● Revised randomization strategy for non-responder to distribute non-responder chronologically throughout study in 1:3 proportion to # of responders randomized ● Revised primary efficacy analysis from Cox proportional-hazard model analysis to stratified log-rank test
    11 Feb 2015
    ● Updated HOMA-IR calculation for insulin resistance ● Removed allowance for repeat of serum creatinine at an unscheduled visit(s) after E5 ● Clarified that if during the Double-Blind Treatment Period the subject discontinued study drug, the investigator should only re-start if it was medically appropriate ● Added statement regarding the maximum duration of atrasentan exposure and maximum atrasentan dose ● Updated the number of study sites to 800 – 900 ● Added additional clarification regarding the randomization strategy of the non-responder arm
    19 May 2017
    ● Updated figures throughout protocol: Revised number of subjects to be enrolled from 4,148 to 3,500; revised responders (UACR reduction ≥ 30% from Baseline) in the Study Diagram from 1,574 to 1,250; revised number of responders from 3,148 to 2,500; extended yearly treatment visits past T48 ● Updated statistical methods: Sample size determination, definition of Baseline, primary efficacy analysis, derivation of safety endpoints, interim analysis ● Updated duration of the Double-Blind Treatment Period from 48 months to approximately 6 years ● Clarified exclusion criterion 19 to re-define premenopausal women are not eligible for study participation

    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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