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    Clinical Trial Results:
    A long-term, randomised, double-blind, placebo-controlled, multinational, multi-centre trial to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes

    Summary
    EudraCT number
    		 2012-002839-28
    Trial protocol
    		 GB   ES   BG   DE   DK   PL   IT  
    Global end of trial date
    15 Mar 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Mar 2017
    First version publication date
    31 Mar 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NN9535-3744
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01720446
    WHO universal trial number (UTN)
    		 U1111-1131-7227
    Sponsors
    Sponsor organisation name
    Novo Nordisk A/S
    Sponsor organisation address
    Novo Allé, Bagsvaerd, Denmark, 2880
    Public contact
    Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
    Scientific contact
    Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.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
    24 Oct 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Mar 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To confirm that treatment with semaglutide does not result in an unacceptable increase in cardiovascular risk as compared to placebo in adults with type 2 diabetes. This is done by demonstrating that the upper limit of the two-sided 95% confidence interval (CI) of the hazard ratio for semaglutide versus placebo is less than 1.8 when comparing time to first occurrence of a major adverse cardiovascular event (MACE).
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki, ICH Good Clinical Practice, EN ISO 14155 Part 1 and 2 and FDA 21 CFR 312.120.
    Background therapy
    		 All participating subjects received the best standard-of-care in addition to the trial products and, to the extent possible, achieved optimal glycaemic control according to local standards (additional glucose lowering medications could be added to the anti-diabetic regimen at the discretion of investigator).
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    21 Feb 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 166
    Country: Number of subjects enrolled
    Australia: 111
    Country: Number of subjects enrolled
    Bulgaria: 101
    Country: Number of subjects enrolled
    Brazil: 105
    Country: Number of subjects enrolled
    Canada: 138
    Country: Number of subjects enrolled
    Germany: 85
    Country: Number of subjects enrolled
    Denmark: 66
    Country: Number of subjects enrolled
    Algeria: 95
    Country: Number of subjects enrolled
    Spain: 85
    Country: Number of subjects enrolled
    United Kingdom: 117
    Country: Number of subjects enrolled
    Israel: 100
    Country: Number of subjects enrolled
    Italy: 80
    Country: Number of subjects enrolled
    Mexico: 165
    Country: Number of subjects enrolled
    Malaysia: 70
    Country: Number of subjects enrolled
    Poland: 98
    Country: Number of subjects enrolled
    Russian Federation: 294
    Country: Number of subjects enrolled
    Thailand: 74
    Country: Number of subjects enrolled
    Turkey: 128
    Country: Number of subjects enrolled
    Taiwan: 82
    Country: Number of subjects enrolled
    United States: 1137
    Worldwide total number of subjects
    3297
    EEA total number of subjects
    632
    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)
    1699
    From 65 to 84 years
    1578
    85 years and over
    20

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The trial was conducted at 229 sites in 20 countries. Country (sites): Algeria (4), Argentina (7), Australia (8), Brazil (8), Bulgaria (5), Canada (13), Denmark (5), Germany (7), Israel (6), Italy (6), Malaysia (6), Mexico (9), Poland (5), Russia (11), Spain (6), Taiwan (4), Thailand (5), Turkey (10), United Kingdom (8) and United States (96).

    Pre-assignment
    Screening details
    		 The trial population was subjects with T2D with inadequate glycaemic control (HbA1c ≥ 7%) at high CV risk. The trial included subjects ≥ 50 years of age at screening with clinical evidence of CV disease and subjects ≥ 60 years of age at screening with subclinical evidence of CV disease.

    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, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Semaglutide 0.5 mg
    Arm description
    		 Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Semaglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Semaglutide solution for injection (1.34 mg/mL in a 1.5 mL pre-filled PDS290 pen-injector) was administered in doses of 0.5 mg once-weekly as subcutaneous (s.c.) injections either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. Subjects started with doses of 0.25 mg semaglutide. After 4 weeks of treatment, the dose was escalated (doubled). Hence, the target dose of 0.5 mg was achieved after 4 weeks of treatment.

    Arm title
    		 Semaglutide 1.0 mg
    Arm description
    		 Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Semaglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Semaglutide solution for injection (1.34 mg/mL in a 1.5 mL pre-filled PDS290 pen-injector) was administered in doses of 1.0 mg once-weekly as subcutaneous (s.c.) injections either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. Subjects started with doses of 0.25 mg semaglutide. After 4 weeks of treatment, the dose was escalated (doubled). Hence, the target dose of 1.0 mg was achieved after 8 weeks of treatment.

    Arm title
    		 Placebo 0.5 mg
    Arm description
    		 Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The composition of the placebo corresponded to that of semaglutide drug product but with absence of the active pharmaceutical ingredient. Placebo solution for injection (1.34 mg/mL in a 1.5 mL pre-filled PDS290 pen-injector) was administered in doses of 0.5 mg once-weekly as subcutaneous (s.c.) injections either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. Subjects started with doses of 0.25 mg semaglutide. After 4 weeks of treatment, the dose was escalated (doubled). Hence, the target dose of 0.5 mg was achieved after 4 weeks of treatment.

    Arm title
    		 Placebo 1.0 mg
    Arm description
    		 Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The composition of the placebo corresponded to that of semaglutide drug product but with absence of the active pharmaceutical ingredient. Placebo solution for injection (1.34 mg/mL in a 1.5 mL pre-filled PDS290 pen-injector) was administered in doses of 1.0 mg once-weekly as subcutaneous (s.c.) injections either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. Subjects started with doses of 0.25 mg semaglutide. After 4 weeks of treatment, the dose was escalated (doubled). Hence, target dose of 1.0 mg was achieved after 8 weeks of treatment.

    Number of subjects in period 1
    		Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Started
    826
    822
    824
    825
    Completed
    812
    811
    804
    805
    Not completed
    14
    11
    20
    20
         Consent withdrawn by subject
    2
    5
    4
    4
         Lost to follow-up
    12
    6
    16
    16

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Semaglutide 0.5 mg
    Reporting group description
    		 Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.

    Reporting group title
    Semaglutide 1.0 mg
    Reporting group description
    		 Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.

    Reporting group title
    Placebo 0.5 mg
    Reporting group description
    		 Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.

    Reporting group title
    Placebo 1.0 mg
    Reporting group description
    		 Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.

    Reporting group values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg Total
    Number of subjects
    		 826 822 824 825 3297
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    		 440 415 419 425 1699
        From 65-84 years
    		 383 400 399 396 1578
        85 years and over
    		 3 7 6 4 20
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.6 ± 7.3 64.7 ± 7.1 64.8 ± 7.6 64.4 ± 7.5 -
    Gender Categorical
    Units: Subjects
        Female
    		 331 304 342 318 1295
        Male
    		 495 518 482 507 2002
    Glycosylated haemoglobin
    Units: percentage of glycosylated haemoglobin
        arithmetic mean (standard deviation)
    		 8.67 ± 1.39 8.73 ± 1.51 8.7 ± 1.49 8.7 ± 1.45 -
    Fasting plasma glucose
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 185.4 ± 66.09 182.9 ± 68.04 185.8 ± 68.23 184.6 ± 63.08 -
    Body weight
    Units: kg
        arithmetic mean (standard deviation)
    		 91.8 ± 20.25 92.86 ± 21.05 91.83 ± 20.35 91.9 ± 20.75 -
    LDL-cholesterol
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 89.62 ± 39.08 89.72 ± 34.49 89.01 ± 38.35 91.14 ± 37.9 -
    HDL-cholesterol
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 45.92 ± 13 44.97 ± 12.42 45.82 ± 12.92 44.61 ± 12.26 -
    Total cholesterol
    Units: mg/dL
        geometric mean (full range (min-max))
    		 165.38 (65.25 to 632.43) 164.96 (79.54 to 562.16) 164.38 (70.27 to 378.38) 165.97 (64.86 to 537.07) -
    Triglycerides
    Units: mg/dL
        geometric mean (full range (min-max))
    		 163.66 (27.59 to 1913.5) 158.93 (10.68 to 3378.44) 162.3 (30.26 to 1438.24) 163 (35.6 to 2435.93) -
    Free fatty acids
    Units: mmol/L
        geometric mean (full range (min-max))
    		 0.83 (0.04 to 3.82) 0.8 (0.04 to 4.2) 0.83 (0.04 to 3.34) 0.81 (0.04 to 4.22) -
    Systolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    		 136.1 ± 17.97 135.8 ± 16.98 135.8 ± 16.16 134.8 ± 17.45 -
    Diastolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    		 77.1 ± 9.78 76.88 ± 10.21 77.54 ± 9.85 76.66 ± 10.21 -
    Pulse rate
    Units: beats/min
        arithmetic mean (standard deviation)
    		 72.69 ± 11.22 71.53 ± 10.86 72.01 ± 10.62 71.95 ± 10.92 -
    Subject analysis sets

    Subject analysis set title
    Semaglutide
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment . Each subject was treated for 104 weeks.

    Subject analysis sets values
    		 Semaglutide Placebo
    Number of subjects
    1648
    1649
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    64.7 ± 7.2
    64.6 ± 7.5
    Gender Categorical
    Units: Subjects
        Female
        Male
    Glycosylated haemoglobin
    Units: percentage of glycosylated haemoglobin
        arithmetic mean (standard deviation)
    ±
    ±
    Fasting plasma glucose
    Units: mg/dL
        arithmetic mean (standard deviation)
    ±
    ±
    Body weight
    Units: kg
        arithmetic mean (standard deviation)
    ±
    ±
    LDL-cholesterol
    Units: mg/dL
        arithmetic mean (standard deviation)
    ±
    ±
    HDL-cholesterol
    Units: mg/dL
        arithmetic mean (standard deviation)
    ±
    ±
    Total cholesterol
    Units: mg/dL
        geometric mean (full range (min-max))
    Triglycerides
    Units: mg/dL
        geometric mean (full range (min-max))
    Free fatty acids
    Units: mmol/L
        geometric mean (full range (min-max))
    Systolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    ±
    ±
    Diastolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    ±
    ±
    Pulse rate
    Units: beats/min
        arithmetic mean (standard deviation)
    ±
    ±

    End points

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    End points reporting groups
    Reporting group title
    Semaglutide 0.5 mg
    Reporting group description
    		 Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.

    Reporting group title
    Semaglutide 1.0 mg
    Reporting group description
    		 Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.

    Reporting group title
    Placebo 0.5 mg
    Reporting group description
    		 Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.

    Reporting group title
    Placebo 1.0 mg
    Reporting group description
    		 Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.

    Subject analysis set title
    Semaglutide
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment . Each subject was treated for 104 weeks.

    Primary: Time from randomisation to first occurrence of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.

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    End point title
    		 Time from randomisation to first occurrence of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.
    End point description
    Proportion of subjects experiencing a first event of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.
    End point type
    Primary
    End point timeframe
    Time from randomisation to first occurrence of an expanded composite cardiovascular outcome.
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    1648
    1649
    Units: proportion of subjects
        number (not applicable)
    6.6
    8.9
    Statistical analysis title
    		 Non-Inferiority
    Statistical analysis description
    The primary endpoint was analysed using a stratified Cox proportional hazards model with treatment group (semaglutide, placebo) as fixed factor. Assuming the same population MACE risk for the semaglutide and placebo groups (i.e., the population HR equals 1), a total minimum of 122 events were needed in order to have at least 90% power to ascertain that the upper two-sided 95% confidence limit for the HR was less than 1.8.
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001 [1]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.95
    Notes
    [1] - The 'p-value' is for the two-sided Wald test of non-inferiority with limit 1.8.
    Statistical analysis title
    		 Superiority
    Statistical analysis description
    A post hoc analysis of superiority of semaglutide versus placebo was performed based on the pre-specified Cox proportional hazard analysis using the two-sided Wald test of no difference, with treatment (semaglutide, placebo) as fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0167 [2]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.95
    Notes
    [2] - The 'p-value' is for the two-sided Wald test of no difference.

    Secondary: Time from randomisation to first occurrence of an expanded composite cardiovascular outcome.

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    End point title
    		 Time from randomisation to first occurrence of an expanded composite cardiovascular outcome.
    End point description
    Subjects experiencing first occurrence of an expanded composite CV outcome (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure).
    End point type
    Secondary
    End point timeframe
    Time from randomisation up to end of follow-up (scheduled at week 109)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    1648
    1649
    Units: proportion of subject
        number (not applicable)
    12.1
    16
    Statistical analysis title
    		 Analysis for an expanded composite CV outcome
    Statistical analysis description
    Analysis was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0016
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.89

    Secondary: Time from randomisation to each individual component of the expanded composite cardiovascular outcome

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    End point title
    		 Time from randomisation to each individual component of the expanded composite cardiovascular outcome
    End point description
    Subjects experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure).
    End point type
    Secondary
    End point timeframe
    Time from randomisation up to end of Follow-up (scheduled at week 109)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    1648
    1649
    Units: proportion of subjects
    number (not applicable)
        Cardiovascular death
    1.6
    1.9
        Non-fatal MI
    2.5
    3.7
        Non-fatal Stroke
    1.5
    2.7
        Revascularisation
    2.6
    4.2
        UAP requiring hospitalisation
    1.1
    1.3
        Hospitalisation for heart failure
    2.7
    2.4
    Statistical analysis title
    		 Analysis for cardiovascular death
    Statistical analysis description
    Analysis for CV death was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9181
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.48
    Statistical analysis title
    		 Analysis for non-fatal myocardial infarction
    Statistical analysis description
    Analysis for non-fatal myocardial infarction was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1194
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.08
    Statistical analysis title
    		 Analysis for non-fatal stroke
    Statistical analysis description
    Analysis for non-fatal stroke was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0438
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 0.99
    Statistical analysis title
    		 Analysis for revascularisation
    Statistical analysis description
    Analysis for revascularisation was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0027
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.86
    Statistical analysis title
    		 Analysis for UA requiring hospitalisation
    Statistical analysis description
    Analysis for 'unstable angina requiring hospitalisation' was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4914
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.44
    Statistical analysis title
    		 Analysis for hospitalisation for heart failure
    Statistical analysis description
    Analysis for hospitalisation for heart failure was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5735
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.61

    Secondary: Time from randomisation to first occurrence of all-cause death, non-fatal MI, or non-fatal stroke

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    End point title
    		 Time from randomisation to first occurrence of all-cause death, non-fatal MI, or non-fatal stroke
    End point description
    Proportion of subjects experiencing a first occurrence of all-cause death, non-fatal MI, or non-fatal stroke.
    End point type
    Secondary
    End point timeframe
    Time from randomisation up to end of follow-up (scheduled at week 109)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    1648
    1649
    Units: proportion of subjects
        number (not applicable)
    7.4
    9.6
    Statistical analysis title
    		 Analysis
    Statistical analysis description
    Analysis for all-cause death, non-fatal MI or non-fatal stroke was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    3297
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0292
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 0.97

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: glycosylated haemoglobin (HbA1c)

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: glycosylated haemoglobin (HbA1c)
    End point description
    Estimated mean change from baseline in glycosylated haemoglobin (HbA1c) to last assessment in the trial during the treatment period.
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: percentage of glycosylated haemoglobin
        least squares mean (standard error)
    -1.09 ± 0.05
    -1.41 ± 0.05
    -0.44 ± 0.05
    -0.36 ± 0.05
    Statistical analysis title
    		 Analysis for HbA1c
    Statistical analysis description
    Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 -0.52
    Statistical analysis title
    		 Analysis for HbA1c
    Statistical analysis description
    Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.19
         upper limit
    		 -0.91

    Secondary: Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: fasting plasma glucose

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    End point title
    		 Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: fasting plasma glucose
    End point description
    Estimated mean change from baseline to last assessment in fasting plasma glucose in the trial during the treatment period.
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: mg/dL
        least squares mean (standard error)
    -1.75 ± 0.12
    -2.11 ± 0.12
    -1.02 ± 0.12
    -0.88 ± 0.12
    Statistical analysis title
    		 Analysis for FPG
    Statistical analysis description
    Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.06
         upper limit
    		 -0.38
    Statistical analysis title
    		 Analysis for FPG
    Statistical analysis description
    Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.56
         upper limit
    		 -0.88

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: body weight

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: body weight [3]
    End point description
    Estimated mean change from baseline to last assessment in body weight in the trial during the treatment period.
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for the two placebo arms are pooled for analysis and thus there are only 3 arms for this endpoint instead of four.
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo
    Number of subjects analysed
    826
    822
    1649
    Units: kg
        least squares mean (standard error)
    -3.57 ± 0.21
    -4.88 ± 0.22
    -0.62 ± 0.15
    Statistical analysis title
    		 Analysis for body weight
    Statistical analysis description
    Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo
    Number of subjects included in analysis
    2475
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -2.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.47
         upper limit
    		 -2.44
    Statistical analysis title
    		 Analysis for body weight
    Statistical analysis description
    Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo
    Number of subjects included in analysis
    2471
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 treatment difference
    Point estimate
    -4.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.78
         upper limit
    		 -3.75

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: lipid profile

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: lipid profile
    End point description
    Estimated ratio to baseline at week 104 during the treatment period in lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides).
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: mg/dL
    least squares mean (standard error)
        Total cholesterol
    0.97 ± 0.01
    0.97 ± 0.01
    1 ± 0.01
    0.99 ± 0.01
        HDL-Cholesterol
    0.99 ± 0.01
    1.01 ± 0.01
    0.99 ± 0.01
    0.97 ± 0.01
        LDL-Cholesterol
    0.97 ± 0.01
    0.98 ± 0.01
    1.01 ± 0.01
    0.99 ± 0.01
        Triglycerides
    0.93 ± 0.01
    0.92 ± 0.01
    0.96 ± 0.01
    0.98 ± 0.01
    Statistical analysis title
    		 Analysis for total cholesterol
    Statistical analysis description
    Analysis for total cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0149
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1
    Statistical analysis title
    		 Analysis for total cholesterol
    Statistical analysis description
    Analysis for total cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.258
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.01
    Statistical analysis title
    		 Analysis for HDL-cholesterol
    Statistical analysis description
    Analysis for HDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8106
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.02
    Statistical analysis title
    		 Analysis for HDL cholesterol
    Statistical analysis description
    Analysis for HDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.06
    Statistical analysis title
    		 Analysis for LDL-cholesterol
    Statistical analysis description
    Analysis for LDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0185
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 0.99
    Statistical analysis title
    		 Analysis for LDL-cholesterol
    Statistical analysis description
    Analysis for LDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5996
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.03
    Statistical analysis title
    		 Analysis for triglycerides
    Statistical analysis description
    Analysis for triglycerides was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1833
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.01
    Statistical analysis title
    		 Analysis for triglycerides
    Statistical analysis description
    Analysis for triglycerides was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0009
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 0.97

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: lipid profile (free fatty acids)

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: lipid profile (free fatty acids)
    End point description
    Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (pulse rate).
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: mmol/L
        least squares mean (standard error)
    0.95 ± 0.02
    0.91 ± 0.01
    0.96 ± 0.02
    0.99 ± 0.02
    Statistical analysis title
    		 Analysis for free fatty acids
    Statistical analysis description
    Analysis for free fatty acids was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7796
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.04
    Statistical analysis title
    		 Analysis for free fatty acids
    Statistical analysis description
    Analysis for free fatty acids was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0003
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 0.96

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: urinary albumin to creatinine ratio

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: urinary albumin to creatinine ratio
    End point description
    Estimated ratio to baseline in urinary albumin to creatinine ratio at week 104 during the treatment period.
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: mg/g
        least squares mean (standard error)
    1.02 ± 0.05
    0.91 ± 0.05
    1.32 ± 0.07
    1.29 ± 0.06
    Statistical analysis title
    		 Analysis for urinary albumin to creatinine ratio
    Statistical analysis description
    Analysis for urinary albumin to creatinine ration was donne using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0003
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.89
    Statistical analysis title
    		 Analysis for urinary albumin to creatinine ratio
    Statistical analysis description
    Analysis for urinary albumin to creatinine ration was donne using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.81

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: vital signs

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: vital signs
    End point description
    Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (diastolic blood pressure and systolic blood pressure).
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: mmHg
    least squares mean (standard error)
        Diastolic blood pressure (mmHg)
    -1.37 ± 0.32
    -1.57 ± 0.32
    -1.42 ± 0.32
    -1.71 ± 0.32
        Systolic blood pressure (mmHg)
    -3.44 ± 0.54
    -5.37 ± 0.54
    -2.17 ± 0.54
    -2.78 ± 0.54
    Statistical analysis title
    		 Analysis for diastolic blood pressure
    Statistical analysis description
    Analysis for diastolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9205
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.83
         upper limit
    		 0.92
    Statistical analysis title
    		 Analysis for diastolic blood pressure
    Statistical analysis description
    Analysis for diastolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7477
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.74
         upper limit
    		 1.03
    Statistical analysis title
    		 Analysis for systolic blood pressure
    Statistical analysis description
    Analysis for systolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0976
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.77
         upper limit
    		 0.23
    Statistical analysis title
    		 Analysis for systolic blood pressure
    Statistical analysis description
    Analysis for systolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0008
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -2.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.09
         upper limit
    		 -1.08

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: vital signs (pulse rate)

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: vital signs (pulse rate)
    End point description
    Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (pulse rate).
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: beats/min
        least squares mean (standard error)
    2.12 ± 0.34
    2.41 ± 0.34
    0.09 ± 0.34
    -0.07 ± 0.34
    Statistical analysis title
    		 Analysis for pulse rate
    Statistical analysis description
    Analysis for pulse rate was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    2.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.07
         upper limit
    		 2.98
    Statistical analysis title
    		 Analysis for pulse rate
    Statistical analysis description
    Analysis for pulse rate was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    2.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.52
         upper limit
    		 3.43

    Secondary: Incidence during the trial in other treatment outcomes: hypoglycaemic events

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    End point title
    		 Incidence during the trial in other treatment outcomes: hypoglycaemic events
    End point description
    Rates (event rate per 100 exposure years) of severe or blood glucose confirmed symptomatic hypoglycaemia defned as an episode that was severe according to the ADA classification or BG confirmed by a PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
    End point type
    Secondary
    End point timeframe
    Week 0 - 109
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: Event rate per 100 exposure years
        number (not applicable)
    37.5
    36.2
    35.3
    39.7
    No statistical analyses for this end point

    Secondary: Incidence during the trial in other treatment outcomes: adverse events

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    End point title
    		 Incidence during the trial in other treatment outcomes: adverse events
    End point description
    Rates (event rate per 100 years of exposure) of treatment emergent adverse events during the treatment period (weeks 0-109)
    End point type
    Secondary
    End point timeframe
    Weeks 0-109
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: Event rate per 100 years of exposure
        number (not applicable)
    330.5
    337
    317.4
    298.3
    No statistical analyses for this end point

    Secondary: Occurrence during the trial in other treatment outcomes: anti-semaglutide antibodies

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    End point title
    		 Occurrence during the trial in other treatment outcomes: anti-semaglutide antibodies [4]
    End point description
    The proportion of subjects that tested positive for anti-semaglutide antibodies at any time point post-baseline during the trial, from week 0 to week 109.
    End point type
    Secondary
    End point timeframe
    Weeks 0-109
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There will not be any antibody data for the two placebo arms. Thus the data is presented for only the 2 semaglutide arms for this endpoint.
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg
    Number of subjects analysed
    826
    822
    Units: proportion of subjects
        number (not applicable)
    1.4
    2.3
    No statistical analyses for this end point

    Secondary: Change from baseline to last assessment in the trial in other treatment outcomes: patient reported outcome (PRO)

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    End point title
    		 Change from baseline to last assessment in the trial in other treatment outcomes: patient reported outcome (PRO)
    End point description
    Estimated mean change from baseline to last assessment in the trial in patient reported outcomes (PRO). PRO questionnaire measured the individual overall health related quality of life namely bodily pain, general health, mental component summary, mental health, physical component summary, physical functioning, role-emotional, role-physical, social functioning and vitality. The PRO scores were transformed to a 0−100 scale with higher scores indicating greater health related quality of life.
    End point type
    Secondary
    End point timeframe
    Week 0, up to week 104
    End point values
    		 Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Number of subjects analysed
    826
    822
    824
    825
    Units: Score
    least squares mean (standard error)
        Bodily pain
    0.66 ± 0.35
    1.82 ± 0.35
    0.16 ± 0.35
    0.35 ± 0.35
        General health
    1.66 ± 0.29
    2.55 ± 0.29
    0.78 ± 0.29
    1.13 ± 0.3
        Mental component summary
    0 ± 0.35
    0.86 ± 0.35
    -0.17 ± 0.35
    -0.11 ± 0.35
        Mental health
    0.48 ± 0.33
    1.08 ± 0.33
    -0.14 ± 0.33
    -0.31 ± 0.33
        Physical component summary
    0.76 ± 0.28
    1.74 ± 0.28
    0.07 ± 0.28
    0.35 ± 0.28
        Physical functioning
    0.42 ± 0.32
    1.12 ± 0.32
    -0.38 ± 0.32
    -0.37 ± 0.33
        Role-emotional
    0.17 ± 0.42
    0.89 ± 0.42
    -0.36 ± 0.42
    -0.05 ± 0.42
        Role-physical
    0.39 ± 0.34
    1.18 ± 0.35
    -0.33 ± 0.35
    0.03 ± 0.35
        Social functioning
    -0.25 ± 0.35
    0.97 ± 0.35
    -0.2 ± 0.36
    -0.17 ± 0.36
        Vitality
    0.29 ± 0.31
    1.55 ± 0.31
    -0.04 ± 0.31
    0.35 ± 0.31
    Statistical analysis title
    		 Analysis for bodily pain
    Statistical analysis description
    Analysis for bodily pain was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3171
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.48
         upper limit
    		 1.47
    Statistical analysis title
    		 Analysis for bodily pain
    Statistical analysis description
    Analysis for bodily pain was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0031
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 2.45
    Statistical analysis title
    		 Analysis for general health
    Statistical analysis description
    Analysis for general health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.035
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.06
         upper limit
    		 1.69
    Statistical analysis title
    		 Analysis for general health
    Statistical analysis description
    Analysis for general health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0007
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2.24
    Statistical analysis title
    		 Analysis for mental component summary
    Statistical analysis description
    Analysis for mental component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7277
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.79
         upper limit
    		 1.13
    Statistical analysis title
    		 Analysis for mental component summary
    Statistical analysis description
    Analysis for mental component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0489
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 1.94
    Statistical analysis title
    		 Analysis for mental health
    Statistical analysis description
    Analysis for mental health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.186
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 1.53
    Statistical analysis title
    		 Analysis for mental health
    Statistical analysis description
    Analysis for mental health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0029
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 2.31
    Statistical analysis title
    		 Analysis for physical component summary
    Statistical analysis description
    Analysis for physical component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0833
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 1.45
    Statistical analysis title
    		 Analysis for physical component summary
    Statistical analysis description
    Analysis for physical component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0004
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 2.17
    Statistical analysis title
    		 Analysis for physical functioning
    Statistical analysis description
    Analysis for physical functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0799
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 1.69
    Statistical analysis title
    		 Analysis for physical functioning
    Statistical analysis description
    Analysis for physical functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0011
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2.4
    Statistical analysis title
    		 Analysis for role emotional
    Statistical analysis description
    Analysis for role emotional was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1431
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.63
         upper limit
    		 1.68
    Statistical analysis title
    		 Analysis for role emotional
    Statistical analysis description
    Analysis for role emotional was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1136
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.22
         upper limit
    		 2.1
    Statistical analysis title
    		 Analysis for role physical
    Statistical analysis description
    Analysis for role physical was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1431
    Method
    		 Mixed models analysis
    Parameter type
    		 treatment difference
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.24
         upper limit
    		 1.67
    Statistical analysis title
    		 Analysis for role physical
    Statistical analysis description
    Analysis for role physical was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0197
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.18
         upper limit
    		 2.11
    Statistical analysis title
    		 Analysis for social fuctioning
    Statistical analysis description
    Analysis for social functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9223
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.03
         upper limit
    		 0.93
    Statistical analysis title
    		 Analysis for social functioning
    Statistical analysis description
    Analysis for social functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0237
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.15
         upper limit
    		 2.13
    Statistical analysis title
    		 Analysis for vitality
    Statistical analysis description
    Analysis for vitality was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 0.5 mg v Placebo 0.5 mg
    Number of subjects included in analysis
    1650
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4523
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 1.19
    Statistical analysis title
    		 Analysis for vitality
    Statistical analysis description
    Analysis for vitality was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
    Comparison groups
    Semaglutide 1.0 mg v Placebo 1.0 mg
    Number of subjects included in analysis
    1647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0064
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 2.07

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events from the first trial-related activity after the subject had signed the informed consent (week -2) until the end of the posttreatment follow-up period (week 109).
    Adverse event reporting additional description
    Safety was assessed using the full analysis set which includes all randomised subjects. Subjects contribute to the evaluation as randomised.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Sema 0.5 mg
    Reporting group description
    		 -

    Reporting group title
    Sema 1.0 mg
    Reporting group description
    		 -

    Reporting group title
    Placebo 0.5 mg
    Reporting group description
    		 -

    Reporting group title
    Placebo 1.0 mg
    Reporting group description
    		 -

    Serious adverse events
    		 Sema 0.5 mg Sema 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    289 / 826 (34.99%)
    276 / 822 (33.58%)
    329 / 824 (39.93%)
    298 / 825 (36.12%)
         number of deaths (all causes)
    30
    32
    32
    28
         number of deaths resulting from adverse events
    3
    3
    2
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Adenocarcinoma gastric
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         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
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Anaplastic astrocytoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    B-cell lymphoma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         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
    B-cell small lymphocytic lymphoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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 cell carcinoma
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign lymph node neoplasm
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Bladder neoplasm
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Bladder papilloma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma recurrent
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Bladder transitional cell carcinoma stage II
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone cancer metastatic
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer in situ
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer stage III
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Bronchial carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Cholangiocarcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cholesteatoma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Chondroma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Choroid melanoma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Colon adenoma
         subjects affected / exposed
    0 / 826 (0.00%)
    4 / 822 (0.49%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Colon neoplasm
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Colorectal cancer
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Endometrial sarcoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Extranodal marginal zone B-cell lymphoma (MALT type)
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder adenocarcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Gastric cancer
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomus tumour
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Growth hormone-producing pituitary tumour
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 adenoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Hepatic cancer
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Invasive breast carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lip neoplasm malignant stage unspecified
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma stage 0
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma stage IV
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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 / 1
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic gastric cancer
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Neoplasm of appendix
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Ovarian epithelial cancer
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ovarian germ cell teratoma benign
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Pancreatic carcinoma stage IV
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Paraganglion neoplasm
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    2 / 825 (0.24%)
         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
    Phaeochromocytoma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Prostate cancer
         subjects affected / exposed
    3 / 826 (0.36%)
    3 / 822 (0.36%)
    4 / 824 (0.49%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer recurrent
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Prostate cancer stage I
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Prostate cancer stage III
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Rectal cancer
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cancer metastatic
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cancer stage I
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Renal cell carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer metastatic
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Thyroid neoplasm
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteric cancer
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Aortic stenosis
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial insufficiency
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Circulatory collapse
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral artery aneurysm
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral artery occlusion
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    3 / 824 (0.36%)
    3 / 825 (0.36%)
         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
    Hypertensive crisis
         subjects affected / exposed
    3 / 826 (0.36%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    4 / 826 (0.48%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    3 / 824 (0.36%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leriche syndrome
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    3 / 826 (0.36%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Peripheral vascular disorder
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Temporal arteritis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Surgical and medical procedures
    Abdominal hernia repair
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angioplasty
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Brachytherapy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Carotid angioplasty
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Carotid artery stent insertion
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid endarterectomy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid revascularisation
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract operation
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary angioplasty
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    4 / 824 (0.49%)
    5 / 825 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary arterial stent insertion
         subjects affected / exposed
    15 / 826 (1.82%)
    8 / 822 (0.97%)
    17 / 824 (2.06%)
    17 / 825 (2.06%)
         occurrences causally related to treatment / all
    1 / 19
    1 / 9
    0 / 18
    2 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery bypass
         subjects affected / exposed
    8 / 826 (0.97%)
    5 / 822 (0.61%)
    14 / 824 (1.70%)
    10 / 825 (1.21%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
    1 / 14
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary revascularisation
         subjects affected / exposed
    11 / 826 (1.33%)
    10 / 822 (1.22%)
    15 / 824 (1.82%)
    9 / 825 (1.09%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 10
    1 / 17
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hospitalisation
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Laparotomy
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mechanical ventilation
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal polypectomy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Percutaneous coronary intervention
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    3 / 824 (0.36%)
    6 / 825 (0.73%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery angioplasty
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery bypass
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stent insertion
         subjects affected / exposed
    1 / 826 (0.12%)
    3 / 822 (0.36%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral endarterectomy
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral revascularisation
         subjects affected / exposed
    2 / 826 (0.24%)
    4 / 822 (0.49%)
    5 / 824 (0.61%)
    9 / 825 (1.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pterygium operation
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Removal of internal fixation
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Renal artery stent placement
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stent placement
         subjects affected / exposed
    2 / 826 (0.24%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon sheath incision
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia repair
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Chest pain
         subjects affected / exposed
    1 / 826 (0.12%)
    3 / 822 (0.36%)
    5 / 824 (0.61%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    2 / 826 (0.24%)
    3 / 822 (0.36%)
    3 / 824 (0.36%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
    0 / 2
    Device malfunction
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug intolerance
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         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
    Generalised oedema
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthermia malignant
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Metaplasia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Microlithiasis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Multi-organ failure
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Necrosis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    8 / 826 (0.97%)
    5 / 822 (0.61%)
    8 / 824 (0.97%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 5
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Pyrexia
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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 / 1
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    3 / 826 (0.36%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cyst
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystocele
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Epididymal tenderness
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Erectile dysfunction
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital haemorrhage
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Prostatic obstruction
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Prostatomegaly
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Testicular cyst
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Vaginal prolapse
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acquired diaphragmatic eventration
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    3 / 826 (0.36%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    3 / 826 (0.36%)
    1 / 822 (0.12%)
    3 / 824 (0.36%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Atelectasis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Bronchitis chronic
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 826 (0.36%)
    5 / 822 (0.61%)
    7 / 824 (0.85%)
    7 / 825 (0.85%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 826 (0.73%)
    5 / 822 (0.61%)
    3 / 824 (0.36%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea at rest
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Epistaxis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperventilation
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Lung cyst
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Pneumonia aspiration
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Pulmonary congestion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Pulmonary embolism
         subjects affected / exposed
    2 / 826 (0.24%)
    4 / 822 (0.49%)
    3 / 824 (0.36%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pulmonary hypertension
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pulmonary mass
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    5 / 825 (0.61%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Respiratory distress
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Respiratory failure
         subjects affected / exposed
    2 / 826 (0.24%)
    3 / 822 (0.36%)
    3 / 824 (0.36%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    3 / 824 (0.36%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Homicidal ideation
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Mental status changes
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    3 / 825 (0.36%)
         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
    Post-traumatic stress disorder
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Schizoaffective disorder
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sleep terror
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriogram coronary
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial test positive
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 alkaline phosphatase increased
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Blood bilirubin increased
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Blood creatinine increased
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Blood glucose fluctuation
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 glucose increased
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Catheterisation cardiac
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Coagulation time prolonged
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram ST segment abnormal
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Electrocardiogram T wave inversion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Electrocardiogram change
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Lipase increased
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic enzymes increased
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Troponin increased
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         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
    Weight decreased
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accident at work
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Alcohol poisoning
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    0 / 825 (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
    Burns third degree
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Contusion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Dural tear
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Failure to anastomose
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    11 / 826 (1.33%)
    5 / 822 (0.61%)
    11 / 824 (1.33%)
    8 / 825 (0.97%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 5
    0 / 11
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Hand fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Head injury
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Hip fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Incorrect dose administered
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Laceration
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Meniscus injury
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Muscle strain
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Near drowning
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 haematoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Postoperative ileus
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Radius fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Road traffic accident
         subjects affected / exposed
    2 / 826 (0.24%)
    4 / 822 (0.49%)
    3 / 824 (0.36%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Seroma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Skin abrasion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Skull fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Spinal compression fracture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Subdural haematoma
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Thermal burn
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Traumatic ulcer
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular graft complication
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Vascular graft occlusion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound necrosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Wrong drug administered
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Phimosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    4 / 826 (0.48%)
    3 / 822 (0.36%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 3
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Acute myocardial infarction
         subjects affected / exposed
    16 / 826 (1.94%)
    13 / 822 (1.58%)
    15 / 824 (1.82%)
    27 / 825 (3.27%)
         occurrences causally related to treatment / all
    1 / 21
    2 / 14
    1 / 15
    2 / 28
         deaths causally related to treatment / all
    1 / 5
    0 / 0
    0 / 0
    0 / 2
    Angina pectoris
         subjects affected / exposed
    9 / 826 (1.09%)
    9 / 822 (1.09%)
    16 / 824 (1.94%)
    12 / 825 (1.45%)
         occurrences causally related to treatment / all
    1 / 9
    1 / 10
    2 / 17
    2 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    13 / 826 (1.57%)
    15 / 822 (1.82%)
    19 / 824 (2.31%)
    22 / 825 (2.67%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 18
    0 / 21
    0 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    3 / 825 (0.36%)
         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
    Atrial fibrillation
         subjects affected / exposed
    14 / 826 (1.69%)
    12 / 822 (1.46%)
    20 / 824 (2.43%)
    18 / 825 (2.18%)
         occurrences causally related to treatment / all
    1 / 16
    2 / 15
    4 / 22
    3 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    4 / 824 (0.49%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Atrioventricular block
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Atrioventricular block complete
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    0 / 825 (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
    Bradycardia
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block right
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    5 / 826 (0.61%)
    2 / 822 (0.24%)
    3 / 824 (0.36%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    0 / 3
    1 / 2
    Cardiac asthma
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    10 / 826 (1.21%)
    10 / 822 (1.22%)
    7 / 824 (0.85%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 11
    2 / 10
    0 / 9
    1 / 4
         deaths causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    4 / 824 (0.49%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    8 / 826 (0.97%)
    4 / 822 (0.49%)
    6 / 824 (0.73%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 4
    2 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    21 / 826 (2.54%)
    14 / 822 (1.70%)
    15 / 824 (1.82%)
    18 / 825 (2.18%)
         occurrences causally related to treatment / all
    2 / 31
    0 / 17
    0 / 19
    1 / 21
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 1
    Cardiac tamponade
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    3 / 824 (0.36%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    1 / 3
    0 / 1
    Cardiomyopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cor pulmonale acute
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    11 / 826 (1.33%)
    9 / 822 (1.09%)
    5 / 824 (0.61%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    1 / 11
    1 / 9
    1 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Coronary artery stenosis
         subjects affected / exposed
    7 / 826 (0.85%)
    2 / 822 (0.24%)
    4 / 824 (0.49%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic cardiomyopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Hypertensive cardiomyopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 cardiomyopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Left ventricular failure
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    4 / 826 (0.48%)
    10 / 822 (1.22%)
    9 / 824 (1.09%)
    12 / 825 (1.45%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 10
    0 / 10
    4 / 14
         deaths causally related to treatment / all
    0 / 1
    1 / 3
    0 / 1
    1 / 4
    Myocardial ischaemia
         subjects affected / exposed
    6 / 826 (0.73%)
    2 / 822 (0.24%)
    3 / 824 (0.36%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 2
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Myocarditis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nodal arrhythmia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary valve stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Silent myocardial infarction
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 826 (0.24%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular asystole
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Ventricular fibrillation
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Ventricular tachyarrhythmia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 826 (0.12%)
    8 / 822 (0.97%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 stem infarction
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Carotid artery stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    3 / 824 (0.36%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar haemorrhage
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Cerebellar syndrome
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 826 (0.24%)
    2 / 822 (0.24%)
    3 / 824 (0.36%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Cerebrospinal fluid leakage
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Cerebrovascular accident
         subjects affected / exposed
    3 / 826 (0.36%)
    3 / 822 (0.36%)
    6 / 824 (0.73%)
    6 / 825 (0.73%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
    0 / 6
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical myelopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Cervical radiculopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic inflammatory demyelinating polyradiculoneuropathy
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coordination abnormal
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Cranial nerve disorder
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic mononeuropathy
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Embolic stroke
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    4 / 824 (0.49%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Headache
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Hypertensive encephalopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Hypoaesthesia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic coma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Hypoglycaemic unconsciousness
         subjects affected / exposed
    5 / 826 (0.61%)
    3 / 822 (0.36%)
    1 / 824 (0.12%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 3
    1 / 1
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial hypotension
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Ischaemic cerebral infarction
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Ischaemic stroke
         subjects affected / exposed
    8 / 826 (0.97%)
    7 / 822 (0.85%)
    16 / 824 (1.94%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    2 / 8
    3 / 8
    0 / 16
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Movement disorder
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Myelitis transverse
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuralgia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parkinsonism
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculitis lumbosacral
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Speech disorder
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 826 (0.24%)
    4 / 822 (0.49%)
    3 / 824 (0.36%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    7 / 826 (0.85%)
    6 / 822 (0.73%)
    10 / 824 (1.21%)
    7 / 825 (0.85%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
    0 / 10
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VIIth nerve paralysis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         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
    VIth nerve disorder
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular parkinsonism
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Visual field defect
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 826 (0.61%)
    4 / 822 (0.49%)
    2 / 824 (0.24%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    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 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Splenic vein thrombosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Splenomegaly
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Thrombocytopenia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Ear and labyrinth disorders
    Deafness neurosensory
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Otosclerosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Tympanic membrane perforation
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Amaurosis fugax
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blindness
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Cataract
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    5 / 825 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract cortical
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Cataract nuclear
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystoid macular oedema
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    4 / 826 (0.48%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 3
    2 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eyelid dermatochalasis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eyelid ptosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Glaucoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Iridocyclitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Macular fibrosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular oedema
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Open angle glaucoma
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Optic ischaemic neuropathy
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal degeneration
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         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
    Retinopathy haemorrhagic
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    2 / 826 (0.24%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal mass
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 826 (0.24%)
    6 / 822 (0.73%)
    2 / 824 (0.24%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 6
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Ascites
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Change of bowel habit
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Colitis ulcerative
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diaphragmatic hernia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Diarrhoea
         subjects affected / exposed
    2 / 826 (0.24%)
    6 / 822 (0.73%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    4 / 6
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Enterocolitis haemorrhagic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Epigastric discomfort
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faeces discoloured
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 disorder
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ileus
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 polyps
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 ulcer
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroduodenitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 826 (0.61%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal ischaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 826 (0.36%)
    3 / 822 (0.36%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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 / 826 (0.00%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    4 / 826 (0.48%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Intestinal ischaemia
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 826 (0.00%)
    3 / 822 (0.36%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal spasm
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Pancreatic cyst
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumoperitoneum
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis haemorrhagic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         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
    Umbilical hernia
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Volvulus of small bowel
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 826 (0.00%)
    3 / 822 (0.36%)
    2 / 824 (0.24%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Cholangitis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    4 / 824 (0.49%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    3 / 826 (0.36%)
    0 / 822 (0.00%)
    6 / 824 (0.73%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    1 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Cholelithiasis
         subjects affected / exposed
    4 / 826 (0.48%)
    2 / 822 (0.24%)
    4 / 824 (0.49%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis obstructive
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Gallbladder necrosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Gallbladder polyp
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 congestion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 failure
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocholecystis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic hepatitis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumobilia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angioedema
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    6 / 826 (0.73%)
    2 / 822 (0.24%)
    3 / 824 (0.36%)
    5 / 825 (0.61%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
    1 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkeratosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Pruritus
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash papular
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Skin necrosis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    3 / 826 (0.36%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    18 / 826 (2.18%)
    6 / 822 (0.73%)
    14 / 824 (1.70%)
    22 / 825 (2.67%)
         occurrences causally related to treatment / all
    1 / 22
    3 / 8
    2 / 14
    5 / 24
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
    0 / 2
    Acute prerenal failure
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anuria
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder trabeculation
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Calculus ureteric
         subjects affected / exposed
    3 / 826 (0.36%)
    3 / 822 (0.36%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Chronic kidney disease
         subjects affected / exposed
    10 / 826 (1.21%)
    5 / 822 (0.61%)
    14 / 824 (1.70%)
    5 / 825 (0.61%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 5
    1 / 17
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Diabetic end stage renal disease
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Glomerulonephritis chronic
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    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 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Nephrolithiasis
         subjects affected / exposed
    2 / 826 (0.24%)
    3 / 822 (0.36%)
    1 / 824 (0.12%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Proteinuria
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal artery arteriosclerosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Renal cyst
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 826 (0.24%)
    3 / 822 (0.36%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    3 / 826 (0.36%)
    1 / 822 (0.12%)
    3 / 824 (0.36%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stag horn calculus
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Urinary bladder polyp
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Urinary incontinence
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Urinary retention
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Thyroid mass
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         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
    Arthritis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         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
    Back pain
         subjects affected / exposed
    1 / 826 (0.12%)
    4 / 822 (0.49%)
    1 / 824 (0.12%)
    6 / 825 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondrolysis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic arthropathy
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Fibromyalgia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Flank pain
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    3 / 826 (0.36%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         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
    Mobility decreased
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 spasms
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Muscular weakness
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    4 / 824 (0.49%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Neck pain
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    6 / 826 (0.73%)
    8 / 822 (0.97%)
    9 / 824 (1.09%)
    10 / 825 (1.21%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
    0 / 9
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Pain in extremity
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue disorder
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Infections and infestations
    Abdominal sepsis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Abscess limb
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute hepatitis B
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspergilloma
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Boutonneuse fever
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Bronchitis
         subjects affected / exposed
    2 / 826 (0.24%)
    2 / 822 (0.24%)
    4 / 824 (0.49%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Campylobacter infection
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    6 / 826 (0.73%)
    3 / 822 (0.36%)
    7 / 824 (0.85%)
    9 / 825 (1.09%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 3
    0 / 7
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Cystitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Diabetic foot infection
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Diverticulitis
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Enteritis infectious
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Enterococcal infection
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Escherichia infection
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Escherichia sepsis
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    4 / 824 (0.49%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis viral
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Gastroenteritis
         subjects affected / exposed
    0 / 826 (0.00%)
    2 / 822 (0.24%)
    4 / 824 (0.49%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Herpes zoster
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Implant site infection
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Incision site infection
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    2 / 825 (0.24%)
         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
    Labyrinthitis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Liver abscess
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Localised infection
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Meningitis bacterial
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    5 / 826 (0.61%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Periumbilical abscess
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Pharyngitis
         subjects affected / exposed
    1 / 826 (0.12%)
    2 / 822 (0.24%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    18 / 826 (2.18%)
    15 / 822 (1.82%)
    22 / 824 (2.67%)
    14 / 825 (1.70%)
         occurrences causally related to treatment / all
    2 / 19
    0 / 16
    0 / 26
    0 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 1
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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 procedural infection
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Post procedural pneumonia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Pulmonary sepsis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Respiratory tract infection
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    7 / 826 (0.85%)
    4 / 822 (0.49%)
    3 / 824 (0.36%)
    7 / 825 (0.85%)
         occurrences causally related to treatment / all
    1 / 7
    1 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    Septic encephalopathy
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    4 / 824 (0.49%)
    3 / 825 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    Sinusitis
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         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
    Soft tissue infection
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Splenic abscess
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Staphylococcal infection
         subjects affected / exposed
    2 / 826 (0.24%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal osteomyelitis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Subcutaneous abscess
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Tooth abscess
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    0 / 825 (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
    Urinary tract infection
         subjects affected / exposed
    9 / 826 (1.09%)
    2 / 822 (0.24%)
    10 / 824 (1.21%)
    6 / 825 (0.73%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 2
    0 / 10
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection pseudomonal
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection staphylococcal
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Urosepsis
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection bacterial
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    3 / 826 (0.36%)
    5 / 822 (0.61%)
    2 / 824 (0.24%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 5
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    4 / 826 (0.48%)
    1 / 822 (0.12%)
    5 / 824 (0.61%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    1 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    2 / 824 (0.24%)
    1 / 825 (0.12%)
         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
    Electrolyte imbalance
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Failure to thrive
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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 / 1
    Fluid overload
         subjects affected / exposed
    2 / 826 (0.24%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    2 / 825 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    3 / 826 (0.36%)
    2 / 822 (0.24%)
    4 / 824 (0.49%)
    4 / 825 (0.48%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    3 / 824 (0.36%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    7 / 826 (0.85%)
    2 / 822 (0.24%)
    5 / 824 (0.61%)
    6 / 825 (0.73%)
         occurrences causally related to treatment / all
    5 / 8
    1 / 2
    5 / 7
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 826 (0.00%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    4 / 824 (0.49%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 826 (0.12%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    0 / 825 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 826 (0.12%)
    1 / 822 (0.12%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    0 / 824 (0.00%)
    1 / 825 (0.12%)
         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
    Metabolic disorder
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    0 / 825 (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
    Obesity
         subjects affected / exposed
    0 / 826 (0.00%)
    0 / 822 (0.00%)
    1 / 824 (0.12%)
    1 / 825 (0.12%)
         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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Sema 0.5 mg Sema 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    573 / 826 (69.37%)
    587 / 822 (71.41%)
    547 / 824 (66.38%)
    524 / 825 (63.52%)
    Investigations
    Amylase increased
         subjects affected / exposed
    31 / 826 (3.75%)
    48 / 822 (5.84%)
    28 / 824 (3.40%)
    28 / 825 (3.39%)
         occurrences all number
    39
    57
    33
    33
    Lipase increased
         subjects affected / exposed
    94 / 826 (11.38%)
    90 / 822 (10.95%)
    66 / 824 (8.01%)
    69 / 825 (8.36%)
         occurrences all number
    121
    123
    76
    83
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    53 / 826 (6.42%)
    46 / 822 (5.60%)
    38 / 824 (4.61%)
    38 / 825 (4.61%)
         occurrences all number
    57
    54
    53
    45
    Headache
         subjects affected / exposed
    54 / 826 (6.54%)
    58 / 822 (7.06%)
    67 / 824 (8.13%)
    74 / 825 (8.97%)
         occurrences all number
    77
    89
    114
    110
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    41 / 826 (4.96%)
    33 / 822 (4.01%)
    44 / 824 (5.34%)
    48 / 825 (5.82%)
         occurrences all number
    46
    34
    46
    55
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    24 / 826 (2.91%)
    42 / 822 (5.11%)
    15 / 824 (1.82%)
    26 / 825 (3.15%)
         occurrences all number
    27
    48
    16
    28
    Eye disorders
    Cataract
         subjects affected / exposed
    55 / 826 (6.66%)
    43 / 822 (5.23%)
    37 / 824 (4.49%)
    45 / 825 (5.45%)
         occurrences all number
    59
    48
    38
    46
    Diabetic retinopathy
         subjects affected / exposed
    46 / 826 (5.57%)
    56 / 822 (6.81%)
    39 / 824 (4.73%)
    38 / 825 (4.61%)
         occurrences all number
    50
    63
    39
    43
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    45 / 826 (5.45%)
    35 / 822 (4.26%)
    33 / 824 (4.00%)
    31 / 825 (3.76%)
         occurrences all number
    54
    40
    37
    36
    Abdominal pain upper
         subjects affected / exposed
    35 / 826 (4.24%)
    42 / 822 (5.11%)
    19 / 824 (2.31%)
    19 / 825 (2.30%)
         occurrences all number
    37
    53
    22
    33
    Constipation
         subjects affected / exposed
    46 / 826 (5.57%)
    79 / 822 (9.61%)
    37 / 824 (4.49%)
    36 / 825 (4.36%)
         occurrences all number
    52
    97
    42
    38
    Diarrhoea
         subjects affected / exposed
    148 / 826 (17.92%)
    148 / 822 (18.00%)
    97 / 824 (11.77%)
    87 / 825 (10.55%)
         occurrences all number
    277
    245
    159
    112
    Dyspepsia
         subjects affected / exposed
    51 / 826 (6.17%)
    63 / 822 (7.66%)
    23 / 824 (2.79%)
    18 / 825 (2.18%)
         occurrences all number
    68
    88
    25
    19
    Nausea
         subjects affected / exposed
    143 / 826 (17.31%)
    179 / 822 (21.78%)
    62 / 824 (7.52%)
    66 / 825 (8.00%)
         occurrences all number
    233
    282
    78
    94
    Vomiting
         subjects affected / exposed
    87 / 826 (10.53%)
    122 / 822 (14.84%)
    42 / 824 (5.10%)
    33 / 825 (4.00%)
         occurrences all number
    128
    170
    51
    41
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    36 / 826 (4.36%)
    32 / 822 (3.89%)
    40 / 824 (4.85%)
    46 / 825 (5.58%)
         occurrences all number
    41
    33
    41
    48
    Renal and urinary disorders
    Microalbuminuria
         subjects affected / exposed
    27 / 826 (3.27%)
    33 / 822 (4.01%)
    46 / 824 (5.58%)
    42 / 825 (5.09%)
         occurrences all number
    30
    35
    51
    45
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    41 / 826 (4.96%)
    35 / 822 (4.26%)
    57 / 824 (6.92%)
    58 / 825 (7.03%)
         occurrences all number
    45
    40
    69
    70
    Back pain
         subjects affected / exposed
    54 / 826 (6.54%)
    49 / 822 (5.96%)
    49 / 824 (5.95%)
    48 / 825 (5.82%)
         occurrences all number
    54
    58
    59
    50
    Pain in extremity
         subjects affected / exposed
    38 / 826 (4.60%)
    29 / 822 (3.53%)
    46 / 824 (5.58%)
    42 / 825 (5.09%)
         occurrences all number
    42
    31
    51
    45
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    46 / 826 (5.57%)
    38 / 822 (4.62%)
    49 / 824 (5.95%)
    51 / 825 (6.18%)
         occurrences all number
    52
    43
    52
    64
    Influenza
         subjects affected / exposed
    51 / 826 (6.17%)
    48 / 822 (5.84%)
    48 / 824 (5.83%)
    46 / 825 (5.58%)
         occurrences all number
    60
    56
    57
    63
    Nasopharyngitis
         subjects affected / exposed
    66 / 826 (7.99%)
    60 / 822 (7.30%)
    78 / 824 (9.47%)
    66 / 825 (8.00%)
         occurrences all number
    91
    77
    99
    84
    Upper respiratory tract infection
         subjects affected / exposed
    53 / 826 (6.42%)
    51 / 822 (6.20%)
    63 / 824 (7.65%)
    65 / 825 (7.88%)
         occurrences all number
    59
    64
    75
    88
    Urinary tract infection
         subjects affected / exposed
    78 / 826 (9.44%)
    71 / 822 (8.64%)
    64 / 824 (7.77%)
    68 / 825 (8.24%)
         occurrences all number
    108
    93
    97
    87
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    86 / 826 (10.41%)
    75 / 822 (9.12%)
    19 / 824 (2.31%)
    9 / 825 (1.09%)
         occurrences all number
    97
    88
    21
    10

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 May 2013
    To accommodate a request from FDA and changes in FDA requirements to the primary objective, the statistical section and other relevant sections were updated accordingly. Additional minor updates were made.
    18 Jun 2014
    The definition of hypoglycaemia was updated including related endpoints, associated statistical analysis and how to report. Additional minor updates for clarification.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/27633186
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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