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    Clinical Trial Results:
    A Multicenter, International, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis

    Summary
    EudraCT number
    2011-001456-11
    Trial protocol
    HU   BE   DK   PL   DE   GB   EE   CZ   ES   LV   LT  
    Global end of trial date
    28 Dec 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    03 Jan 2018
    First version publication date
    03 Jan 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20070337
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01575834
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Amgen Inc
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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
    28 Dec 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Dec 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to determine if treatment with romosozumab is effective in preventing fractures in women with postmenopausal osteoporosis
    Protection of trial subjects
    This study was conducted in accordance with applicable local, Food and Drug Administration, and International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. The study protocol, subject information, and informed consent form were reviewed and approved by the independent ethics committee (IEC) or institutional review board (IRB) for each study center. All subjects provided written informed consent before any protocol-specific screening procedures or any investigational products were administered and after the aims, methods, anticipated benefits, and potential hazards of the study were adequately explained.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Mar 2012
    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
    Spain: 61
    Country: Number of subjects enrolled
    Switzerland: 34
    Country: Number of subjects enrolled
    United Kingdom: 398
    Country: Number of subjects enrolled
    United States: 132
    Country: Number of subjects enrolled
    Argentina: 177
    Country: Number of subjects enrolled
    Australia: 25
    Country: Number of subjects enrolled
    Belgium: 26
    Country: Number of subjects enrolled
    Brazil: 816
    Country: Number of subjects enrolled
    Canada: 63
    Country: Number of subjects enrolled
    Colombia: 1822
    Country: Number of subjects enrolled
    Czech Republic: 334
    Country: Number of subjects enrolled
    Denmark: 334
    Country: Number of subjects enrolled
    Dominican Republic: 173
    Country: Number of subjects enrolled
    Estonia: 110
    Country: Number of subjects enrolled
    Germany: 67
    Country: Number of subjects enrolled
    Hong Kong: 231
    Country: Number of subjects enrolled
    Hungary: 203
    Country: Number of subjects enrolled
    India: 106
    Country: Number of subjects enrolled
    Japan: 492
    Country: Number of subjects enrolled
    Latvia: 51
    Country: Number of subjects enrolled
    Lithuania: 112
    Country: Number of subjects enrolled
    Mexico: 96
    Country: Number of subjects enrolled
    New Zealand: 34
    Country: Number of subjects enrolled
    Poland: 1241
    Country: Number of subjects enrolled
    Romania: 42
    Worldwide total number of subjects
    7180
    EEA total number of subjects
    2979
    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)
    1525
    From 65 to 84 years
    5439
    85 years and over
    216

    Subject disposition

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    Recruitment
    Recruitment details
    This study was conducted at 222 centers in Europe, Central/Latin America, Asia, North America, and Australia/New Zealand. The first participant enrolled on 15 March 2012 and the last participant enrolled on 06 December 2013.

    Pre-assignment
    Screening details
    Participants were randomized 1:1 to receive either romosozumab 210 mg or matched placebo for the 12-month, double-blind, placebo-controlled period. Randomization was stratified by age (< 75 years, ≥ 75 years) and prevalent vertebral fracture (yes, no), as determined by site staff at randomization based on local reading of the spine X-ray.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo/Denosumab
    Arm description
    Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once a month

    Investigational medicinal product name
    Denosumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 6 months

    Arm title
    Romosozumab/Denosumab
    Arm description
    Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.
    Arm type
    Experimental

    Investigational medicinal product name
    Denosumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 6 months

    Investigational medicinal product name
    Romosozumab
    Investigational medicinal product code
    AMG 785
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once a month

    Number of subjects in period 1
    Placebo/Denosumab Romosozumab/Denosumab
    Started
    3591
    3589
    Received Double-blind Treatment
    3582
    3575
    Completed Double-blind Period
    3205
    3185
    Completed 24-month Study Period
    3032
    2994
    Completed
    2892
    2851
    Not completed
    699
    738
         Death
    81
    74
         Other
    70
    70
         Requirement for alternative therapy
    2
    4
         Noncompliance
    52
    27
         Administrative decision
    15
    33
         Ineligibility determined
    5
    8
         Adverse event, non-fatal
    63
    61
         Consent withdrawn by subject
    352
    390
         Protocol deviation
    4
    3
         Lost to follow-up
    55
    68

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo/Denosumab
    Reporting group description
    Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group title
    Romosozumab/Denosumab
    Reporting group description
    Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group values
    Placebo/Denosumab Romosozumab/Denosumab Total
    Number of subjects
    3591 3589 7180
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    757 768 1525
        From 65-84 years
    2727 2712 5439
        85 years and over
    107 109 216
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    70.8 ± 6.9 70.9 ± 7.0 -
    Gender Categorical
    Units: Subjects
        Female
    3591 3589 7180
        Male
    0 0 0
    Race
    Units: Subjects
        White
    2052 2063 4115
        Asian
    441 425 866
        Black or African American
    74 77 151
        American Indian/Alaska Native
    63 64 127
        Native Hawaiian/Other Pacific Islander
    1 0 1
        Multiple
    59 60 119
        Other
    901 900 1801
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    1416 1427 2843
        Not Hispanic or Latino
    2175 2162 4337
    Prevalent Vertebral Fracture Strata per Randomization
    Strata per randomization for prevalent fracture were based on local reading of baseline spine radiographs.
    Units: Subjects
        Yes
    205 204 409
        No
    3386 3385 6771
    Age Strata per Randomization
    Units: Subjects
        < 75 years
    2471 2470 4941
        ≥ 75 years
    1120 1119 2239

    End points

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    End points reporting groups
    Reporting group title
    Placebo/Denosumab
    Reporting group description
    Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group title
    Romosozumab/Denosumab
    Reporting group description
    Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Primary: Percentage of Participants with New Vertebral Fracture Through Month 12

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    End point title
    Percentage of Participants with New Vertebral Fracture Through Month 12
    End point description
    New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: • Grade 0 (Normal) = no fracture; • Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); • Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; • Grade 3 (Severe) = severe fracture, > 40% reduction in anterior, middle, and/or posterior height. The primary analysis set for vertebral fractures includes all subjects with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 12 months, including subjects with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
    End point type
    Primary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3322
    3321
    Units: percentage of participants
        number (not applicable)
    1.8
    0.5
    Statistical analysis title
    Analysis of New Vertebral Fracture To Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6643
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    < 0.001 [2]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.15
         upper limit
    0.47
    Notes
    [1] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [2] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Primary: Percentage of Participants with New Vertebral Fracture Through Month 24

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    End point title
    Percentage of Participants with New Vertebral Fracture Through Month 24
    End point description
    New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: • Grade 0 (Normal) = no fracture; • Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); • Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; • Grade 3 (Severe) = severe fracture, > 40% reduction in anterior, middle, and/or posterior height. The primary analysis set for vertebral fractures includes all subjects with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 24 months, including subjects with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
    End point type
    Primary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3327
    3325
    Units: percentage of participants
        number (not applicable)
    2.5
    0.6
    Statistical analysis title
    Analysis of New Vertebral Fracture To Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6652
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    < 0.001 [4]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.15
         upper limit
    0.39
    Notes
    [3] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [4] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percentage of Participants with a Clinical Fracture Through Month 12

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    End point title
    Percentage of Participants with a Clinical Fracture Through Month 12
    End point description
    Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set consisted of all randomized participants. Last observation carried forward imputation (LOCF) was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    2.5
    1.6
    Statistical analysis title
    Analysis of Clinical Fracture Through Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    = 0.008 [6]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.46
         upper limit
    0.89
    Notes
    [5] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [6] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Nonvertebral Fracture Through Month 12

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    End point title
    Percentage of Participants with a Nonvertebral Fracture Through Month 12
    End point description
    A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    2.1
    1.6
    Statistical analysis title
    Analysis of Nonvertebral Fracture Through Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [7]
    P-value
    = 0.096 [8]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.53
         upper limit
    1.05
    Notes
    [7] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [8] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Nonvertebral Fracture Through Month 24

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    End point title
    Percentage of Participants with a Nonvertebral Fracture Through Month 24
    End point description
    A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date as recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set was used for the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    3.6
    2.7
    Statistical analysis title
    Analysis of Nonvertebral Fracture Through Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [9]
    P-value
    = 0.057 [10]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.57
         upper limit
    0.97
    Notes
    [9] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [10] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Clinical Fracture Through Month 24

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    End point title
    Percentage of Participants with a Clinical Fracture Through Month 24
    End point description
    Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded. The full analysis set with LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    4.1
    2.8
    Statistical analysis title
    Analysis of Clinical Fracture Through Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [11]
    P-value
    = 0.096 [12]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.52
         upper limit
    0.87
    Notes
    [11] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [12] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Nonvertebral Fracture Through Month 12

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    End point title
    Percentage of Participants with a Major Nonvertebral Fracture Through Month 12
    End point description
    A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip. The full analysis set was used for the analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    1.5
    1.0
    Statistical analysis title
    Analysis of Major Nonvertebral Fracture
    Statistical analysis description
    Analysis of major nonvertebral fracture through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [13]
    P-value
    = 0.096 [14]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.44
         upper limit
    1.02
    Notes
    [13] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [14] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Nonvertebral Fracture Through Month 24

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    End point title
    Percentage of Participants with a Major Nonvertebral Fracture Through Month 24
    End point description
    A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip. The full analysis set was used for the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    2.8
    1.9
    Statistical analysis title
    Analysis of Major Nonvertebral Fracture
    Statistical analysis description
    Analysis of major nonvertebral fracture through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [15]
    P-value
    = 0.096 [16]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.49
         upper limit
    0.91
    Notes
    [15] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [16] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 12

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    End point title
    Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 12
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. The primary analysis set for vertebral fractures with LOCF imputation was used for the analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3322
    3321
    Units: percentage of participants
        number (not applicable)
    1.8
    0.5
    Statistical analysis title
    Analysis of New or Worsening Vertebral Fracture
    Statistical analysis description
    Analysis of new or worsening vertebral fracture through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6643
    Analysis specification
    Pre-specified
    Analysis type
    superiority [17]
    P-value
    = 0.096 [18]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.17
         upper limit
    0.49
    Notes
    [17] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [18] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 24

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    End point title
    Percentage of Participants with a New or Worsening Vertebral Fracture Through Month 24
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. The primary analysis set for vertebral fractures with LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3327
    3325
    Units: percentage of participants
        number (not applicable)
    2.5
    0.7
    Statistical analysis title
    Analysis of New or Worsening Vertebral Fracture
    Statistical analysis description
    Analysis of new or worsening vertebral fracture through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6652
    Analysis specification
    Pre-specified
    Analysis type
    superiority [19]
    P-value
    = 0.096 [20]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.16
         upper limit
    0.41
    Notes
    [19] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [20] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test

    Secondary: Percentage of Participants with a Hip Fracture Through Month 12

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    End point title
    Percentage of Participants with a Hip Fracture Through Month 12
    End point description
    Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    0.4
    0.2
    Statistical analysis title
    Analysis of Hip Fracture Through Month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [21]
    P-value
    = 0.18 [22]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.22
         upper limit
    1.35
    Notes
    [21] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [22] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Hip Fracture Through Month 24

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    End point title
    Percentage of Participants with a Hip Fracture Through Month 24
    End point description
    Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    0.6
    0.3
    Statistical analysis title
    Analysis of Hip Fracture Through Month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority [23]
    P-value
    = 0.12 [24]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.24
         upper limit
    1.04
    Notes
    [23] - A fixed-sequence testing procedure was used for multiplicity adjustment of the coprimary and a subset of secondary efficacy endpoints to maintain the overall significance level at 0.05.
    [24] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Osteoporotic Fracture Through Month 12

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    End point title
    Percentage of Participants with a Major Osteoporotic Fracture Through Month 12
    End point description
    Major osteoporotic fractures included hip, forearm, or humerus fractures that were not associated with a pathologic fracture regardless of trauma severity, and clinical vertebral fractures. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    1.8
    1.1
    Statistical analysis title
    Analysis of Major Osteoporotic Fracture
    Statistical analysis description
    Analysis of major osteoporotic fracture through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012 [25]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    0.9
    Notes
    [25] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with a Major Osteoporotic Fracture Through Month 24

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    End point title
    Percentage of Participants with a Major Osteoporotic Fracture Through Month 24
    End point description
    Major osteoporotic fractures included hip, forearm, or humerus fractures that were not associated with a pathologic fracture regardless of trauma severity, and clinical vertebral fractures. The full analysis set was used for this analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3591
    3589
    Units: percentage of participants
        number (not applicable)
    3.1
    1.9
    Statistical analysis title
    Analysis of Major Osteoporotic Fracture
    Statistical analysis description
    Analysis of major osteoporotic fracture through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    7180
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002 [26]
    Method
    Cox proportional hazards
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.46
         upper limit
    0.84
    Notes
    [26] - Cox proportional hazards model adjusting for age and prevalent vertebral fracture stratification variables.

    Secondary: Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 12

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    End point title
    Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 12
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit. The primary analysis set for vertebral fractures with LOCF imputation was used for the analysis.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3322
    3321
    Units: percentage of participants
        number (not applicable)
    0.3
    0.03
    Statistical analysis title
    Statistical Analysis
    Statistical analysis description
    Analysis of multiple new or worsening vertebral fractures through month 12
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6643
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011 [27]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.01
         upper limit
    0.87
    Notes
    [27] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 24

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    End point title
    Percentage of Participants with Multiple New or Worsening Vertebral Fractures Through Month 24
    End point description
    A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit. The primary analysis set for vertebral fractures with LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3327
    3325
    Units: percentage of participants
        number (not applicable)
    0.5
    0.03
    Statistical analysis title
    Statistical Analysis
    Statistical analysis description
    Analysis of multiple new or worsening vertebral fractures through month 24
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6652
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [28]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.01
         upper limit
    0.44
    Notes
    [28] - Based on logistic regression model adjusted for age and prevalent vertebral fracture stratification variables; p-value based on score test.

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Lumbar Spine at Month 12

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    End point title
    Percent Change from Baseline in Bone Mineral Density at the Lumbar Spine at Month 12
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and month 12
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3148
    3151
    Units: percent change
        least squares mean (standard error)
    0.4 ± 0.1
    13.1 ± 0.1
    Statistical analysis title
    Analysis of Lumbar Spine BMD at Month 12
    Statistical analysis description
    The treatment comparison of BMD at the lumbar spine was analyzed using an analysis of covariance (ANCOVA) model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6299
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    12.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.4
         upper limit
    12.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline In Bone Mineral Density at the Lumbar Spine at Month 24

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    End point title
    Percent Change from Baseline In Bone Mineral Density at the Lumbar Spine at Month 24
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Month 24
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    2877
    2861
    Units: percent change
        least squares mean (standard error)
    5.5 ± 0.1
    16.6 ± 0.1
    Statistical analysis title
    Analysis of Lumbar Spine BMD at Month 24
    Statistical analysis description
    The treatment comparison of BMD at the lumbar spine was analyzed using an analysis of covariance (ANCOVA) model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    5738
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    11.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.8
         upper limit
    11.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 12

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    End point title
    Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 12
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and month 12
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3210
    3197
    Units: percent change
        least squares mean (standard error)
    0.3 ± 0.1
    6.0 ± 0.1
    Statistical analysis title
    Analysis of Total Hip BMD at Month 12
    Statistical analysis description
    The treatment comparison of BMD at the total hip was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6407
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    5.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.6
         upper limit
    6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 24

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    End point title
    Percent Change from Baseline in Bone Mineral Density at the Total Hip at Month 24
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and month 24
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    2918
    2903
    Units: percent change
        least squares mean (standard error)
    3.2 ± 0.1
    8.5 ± 0.1
    Statistical analysis title
    Analysis of Total Hip BMD at Month 24
    Statistical analysis description
    The treatment comparison of BMD at the total hip was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    5821
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    5.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.1
         upper limit
    5.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 12

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    End point title
    Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 12
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and month 12
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    3210
    3197
    Units: percent change
        least squares mean (standard error)
    0.3 ± 0.1
    5.5 ± 0.1
    Statistical analysis title
    Analysis of Femoral Neck BMD at Month 12
    Statistical analysis description
    The treatment comparison of BMD at the femoral neck was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    6407
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    5.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.9
         upper limit
    5.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 24

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    End point title
    Percent Change from Baseline in Bone Mineral Density at the Femoral Neck at Month 24
    End point description
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. The primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and month 24
    End point values
    Placebo/Denosumab Romosozumab/Denosumab
    Number of subjects analysed
    2918
    2903
    Units: percent change
        least squares mean (standard error)
    2.3 ± 0.1
    7.3 ± 0.1
    Statistical analysis title
    Analysis of Femoral Neck BMD at Month 24
    Statistical analysis description
    The treatment comparison of BMD at the femoral neck was analyzed using an ANCOVA model which included treatment, age and prevalent vertebral fracture stratification variables, and baseline value of the endpoint, machine type and machine type-by-baseline value interaction.
    Comparison groups
    Placebo/Denosumab v Romosozumab/Denosumab
    Number of subjects included in analysis
    5821
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    4.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.7
         upper limit
    5.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Double-blind treatment period: 12 months; Overall study: 36 months
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    12-Month Double-blind Period: Placebo
    Reporting group description
    Participants received placebo subcutaneous injections once a month for 12 months.

    Reporting group title
    12-Month Double-blind Period: Romosozumab
    Reporting group description
    Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months.

    Reporting group title
    36-Month Study Period: Placebo/Denosumab
    Reporting group description
    Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Reporting group title
    36-Month Study Period: Romosozumab/Denosumab
    Reporting group description
    Participants received romosozumab 210 mg subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

    Serious adverse events
    12-Month Double-blind Period: Placebo 12-Month Double-blind Period: Romosozumab 36-Month Study Period: Placebo/Denosumab 36-Month Study Period: Romosozumab/Denosumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    314 / 3576 (8.78%)
    344 / 3581 (9.61%)
    733 / 3576 (20.50%)
    728 / 3581 (20.33%)
         number of deaths (all causes)
    24
    29
    85
    72
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Cataract operation complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    Eye injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eyelid injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    6 / 3576 (0.17%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    8 / 3576 (0.22%)
    3 / 3581 (0.08%)
    14 / 3576 (0.39%)
    11 / 3581 (0.31%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
    0 / 14
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    7 / 3576 (0.20%)
    4 / 3581 (0.11%)
    19 / 3576 (0.53%)
    9 / 3581 (0.25%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    0 / 19
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    4 / 3576 (0.11%)
    4 / 3581 (0.11%)
    8 / 3576 (0.22%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stoma complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
    3 / 3576 (0.08%)
    6 / 3581 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    8 / 3576 (0.22%)
    8 / 3581 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Internal injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post concussion syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Postoperative adhesion
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative delirium
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural hypotension
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radial head dislocation
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    5 / 3576 (0.14%)
    3 / 3581 (0.08%)
    17 / 3576 (0.48%)
    14 / 3581 (0.39%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 17
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    3 / 3576 (0.08%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stoma site ischaemia
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    Subdural haematoma
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    4 / 3576 (0.11%)
    4 / 3581 (0.11%)
    7 / 3576 (0.20%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
    12 / 3576 (0.34%)
    8 / 3581 (0.22%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 12
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine dehiscence
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound evisceration
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound necrosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood lactic acid increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood pressure decreased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Body mass index increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric pH decreased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza B virus test positive
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    3 / 3576 (0.08%)
    0 / 3581 (0.00%)
    5 / 3576 (0.14%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 3576 (0.11%)
    6 / 3581 (0.17%)
    10 / 3576 (0.28%)
    16 / 3581 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 11
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    Adams-Stokes syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    3 / 3576 (0.08%)
    3 / 3581 (0.08%)
    5 / 3576 (0.14%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 1
    Angina unstable
         subjects affected / exposed
    3 / 3576 (0.08%)
    6 / 3581 (0.17%)
    9 / 3576 (0.25%)
    10 / 3581 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
    0 / 9
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease mixed
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    4 / 3576 (0.11%)
    6 / 3581 (0.17%)
    18 / 3576 (0.50%)
    17 / 3581 (0.47%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
    1 / 20
    0 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    3 / 3576 (0.08%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 2
    Cardiac failure
         subjects affected / exposed
    1 / 3576 (0.03%)
    5 / 3581 (0.14%)
    7 / 3576 (0.20%)
    10 / 3581 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 7
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    Cardiac failure chronic
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    5 / 3576 (0.14%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    4 / 3576 (0.11%)
    7 / 3581 (0.20%)
    8 / 3576 (0.22%)
    10 / 3581 (0.28%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 8
    1 / 9
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    5 / 3576 (0.14%)
    4 / 3581 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 5
    0 / 3
    Cardiogenic shock
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Cor pulmonale
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    3 / 3576 (0.08%)
    4 / 3581 (0.11%)
    7 / 3576 (0.20%)
    7 / 3581 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 7
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heart valve incompetence
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Low cardiac output syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
    9 / 3576 (0.25%)
    8 / 3581 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 9
    0 / 8
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
    0 / 3
    Myocardial ischaemia
         subjects affected / exposed
    4 / 3576 (0.11%)
    3 / 3581 (0.08%)
    7 / 3576 (0.20%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paroxysmal atrioventricular block
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prinzmetal angina
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    4 / 3581 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    3 / 3576 (0.08%)
    0 / 3581 (0.00%)
    5 / 3576 (0.14%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Dermoid cyst
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    4 / 3576 (0.11%)
    2 / 3581 (0.06%)
    9 / 3576 (0.25%)
    4 / 3581 (0.11%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia of chronic disease
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aplastic anaemia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypocoagulable state
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    4 / 3581 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pernicious anaemia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amyotrophic lateral sclerosis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arachnoid cyst
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal ganglia stroke
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain stem ischaemia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid arteriosclerosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar ischaemia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cerebral infarction
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    7 / 3576 (0.20%)
    4 / 3581 (0.11%)
    9 / 3576 (0.25%)
    14 / 3581 (0.39%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 11
    0 / 14
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical myelopathy
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervicobrachial syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervicogenic headache
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic coma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolic cerebral infarction
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
    1 / 3576 (0.03%)
    5 / 3581 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic cerebral infarction
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    3 / 3576 (0.08%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Haemorrhagic transformation stroke
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Headache
         subjects affected / exposed
    3 / 3576 (0.08%)
    0 / 3581 (0.00%)
    4 / 3576 (0.11%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Internal carotid artery kinking
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    9 / 3576 (0.25%)
    13 / 3581 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 10
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbosacral radiculopathy
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meralgia paraesthetica
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Motor dysfunction
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis relapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nerve root compression
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nystagmus
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paralysis recurrent laryngeal nerve
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paresis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post-traumatic headache
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ruptured cerebral aneurysm
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    Sciatica
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    5 / 3576 (0.14%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stupor
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 3576 (0.08%)
    4 / 3581 (0.11%)
    7 / 3576 (0.20%)
    9 / 3581 (0.25%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 3576 (0.03%)
    4 / 3581 (0.11%)
    6 / 3576 (0.17%)
    13 / 3581 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 7
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular encephalopathy
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Age-related macular degeneration
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angle closure glaucoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blindness unilateral
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    5 / 3576 (0.14%)
    4 / 3581 (0.11%)
    14 / 3576 (0.39%)
    13 / 3581 (0.36%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
    0 / 16
    1 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystoid macular oedema
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lens disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Posterior capsule rupture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uveitis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Acute vestibular syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deafness unilateral
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoacusis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniere's disease
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    3 / 3576 (0.08%)
    2 / 3581 (0.06%)
    5 / 3576 (0.14%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vestibular ataxia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal incarcerated hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    3 / 3576 (0.08%)
    4 / 3581 (0.11%)
    9 / 3576 (0.25%)
    10 / 3581 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
    0 / 9
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coeliac disease
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    0 / 3576 (0.00%)
    4 / 3581 (0.11%)
    2 / 3576 (0.06%)
    5 / 3581 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fistula of small intestine
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    3 / 3576 (0.08%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal angiodysplasia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    6 / 3576 (0.17%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal hypomotility
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernial eventration
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
    3 / 3576 (0.08%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Intestinal perforation
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal ulcer
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Mallory-Weiss syndrome
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesenteric artery thrombosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic cyst
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic cyst rupture
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic fistula
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    6 / 3581 (0.17%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritoneal adhesions
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal prolapse
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reflux gastritis
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toothache
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    3 / 3576 (0.08%)
    2 / 3581 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    3 / 3581 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
    1 / 3576 (0.03%)
    5 / 3581 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute prerenal failure
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocalyx
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    2 / 3576 (0.06%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
    2 / 3576 (0.06%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal infarct
         subjects affected / exposed
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
    0 / 3576 (0.00%)
    1 / 3581 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal injury
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress urinary incontinence
         subjects affected / exposed
    0 / 3576 (0.00%)
    0 / 3581 (0.00%)
    1 / 3576 (0.03%)
    0 / 3581 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteric perforation