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    Clinical Trial Results:
    A Clinical Outcomes Study to Compare the Incidence of Major Adverse Cardiovascular Events in Subjects Presenting with Acute Coronary Syndrome Treated with Losmapimod Compared to Placebo (PM1116197) Losmapimod To Inhibit p38 MAP kinase as a Therapeutic target and modify outcomes after an acute coronary syndromE (LATITUDE)-TIMI 60

    Summary
    EudraCT number
    		 2013-000657-50
    Trial protocol
    		 SE   NL   IT   DE   BE   SK   DK   ES   NO   GB   CZ   HU   EE   GR   PL   BG   RO  
    Global end of trial date
    14 Dec 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 May 2016
    First version publication date
    13 May 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PM1116197
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02145468
    WHO universal trial number (UTN)
    		 U1111-1150-5007
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    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
    18 Feb 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Dec 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to evaluate the efficacy of oral losmapimod 7.5 mg BID compared to placebo when added to standard of care in subjects with acute coronary syndrome (ACS) on the time to first occurrence of adjudicated Major Adverse Cardiovascular Events (MACE; defined as CV death, MI, or severe recurrent ischemia [SRI-UR]) through 12 weeks of therapy.
    Protection of trial subjects
    Not applicable
    Background therapy
    		 Investigators managed the subjects according to standard of care, following local prescribing information. Close adherence to professional society guidelines for standard of care therapies in ACS was emphasized during study conduct, including anti-platelet therapy, statin medications, use of appropriate revascularization, ACE inhibitors and beta blockers.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Jun 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 130
    Country: Number of subjects enrolled
    Canada: 52
    Country: Number of subjects enrolled
    Chile: 33
    Country: Number of subjects enrolled
    Hong Kong: 14
    Country: Number of subjects enrolled
    Korea, Republic of: 62
    Country: Number of subjects enrolled
    Mexico: 12
    Country: Number of subjects enrolled
    New Zealand: 67
    Country: Number of subjects enrolled
    Philippines: 16
    Country: Number of subjects enrolled
    Russian Federation: 233
    Country: Number of subjects enrolled
    South Africa: 25
    Country: Number of subjects enrolled
    Taiwan: 54
    Country: Number of subjects enrolled
    Thailand: 30
    Country: Number of subjects enrolled
    Ukraine: 90
    Country: Number of subjects enrolled
    United States: 417
    Country: Number of subjects enrolled
    Israel: 38
    Country: Number of subjects enrolled
    Argentina: 42
    Country: Number of subjects enrolled
    Netherlands: 223
    Country: Number of subjects enrolled
    Norway: 39
    Country: Number of subjects enrolled
    Poland: 215
    Country: Number of subjects enrolled
    Romania: 58
    Country: Number of subjects enrolled
    Slovakia: 231
    Country: Number of subjects enrolled
    Spain: 229
    Country: Number of subjects enrolled
    Sweden: 92
    Country: Number of subjects enrolled
    United Kingdom: 62
    Country: Number of subjects enrolled
    Belgium: 72
    Country: Number of subjects enrolled
    Bulgaria: 73
    Country: Number of subjects enrolled
    Czech Republic: 228
    Country: Number of subjects enrolled
    Denmark: 51
    Country: Number of subjects enrolled
    Estonia: 99
    Country: Number of subjects enrolled
    France: 97
    Country: Number of subjects enrolled
    Germany: 186
    Country: Number of subjects enrolled
    Greece: 76
    Country: Number of subjects enrolled
    Hungary: 87
    Country: Number of subjects enrolled
    Italy: 56
    Worldwide total number of subjects
    3489
    EEA total number of subjects
    2174
    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)
    1437
    From 65 to 84 years
    1942
    85 years and over
    110

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was planned in 2 parts (Part A, N=3500 & Part B, N=22,000). Upon completion of Part A, a decision was made not to progress to Part B because of lack of efficacy. 3503 participants (par.) were randomized to Part A. 14 par. were excluded due to concerns over data integrity. 3489 par. were randomized & included in the ITT Population.

    Pre-assignment
    Screening details
    		 Eligible: ≥ 35 yrs & hospitalized with type 1 MI & 1 additional predictor of CV risk. Excluded: unstable, known liver disease, life-threatening or opportunistic infection, severe renal impairment, NYHA III/ IV or Killip III/ IV CHF. All participants were followed through the end of the study unless they withdrew consent to participate.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received matching placebo twice daily (BID) according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral doses to be taken twice daily with or without food and swallowed whole (not chewed).

    Arm title
    		 Losmapimod 7.5 mg BID
    Arm description
    		 Participants received oral losmapimod 7.5 milligrams (mg) BID according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losmapimod
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral doses to be taken twice daily with or without food and swallowed whole (not chewed).

    Number of subjects in period 1
    		Placebo Losmapimod 7.5 mg BID
    Started
    1758
    1731
    Completed
    1753
    1722
    Not completed
    5
    9
         Consent withdrawn by subject
    5
    8
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo twice daily (BID) according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.

    Reporting group title
    Losmapimod 7.5 mg BID
    Reporting group description
    		 Participants received oral losmapimod 7.5 milligrams (mg) BID according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.

    Reporting group values
    		 Placebo Losmapimod 7.5 mg BID Total
    Number of subjects
    		 1758 1731 3489
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.5 ± 9.72 66.7 ± 10 -
    Gender categorical
    Units: Subjects
        Female
    		 532 500 1032
        Male
    		 1226 1231 2457
    Race, customized
    Units: Subjects
        American Indian or Alaskan Native
    		 8 8 16
        Asian
    		 99 105 204
        Black
    		 25 20 45
        White
    		 1616 1585 3201
        Native Hawaiian or Other Pacific Islander
    		 5 10 15
        Mixed Race
    		 2 3 5
        Missing
    		 3 0 3

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo twice daily (BID) according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.

    Reporting group title
    Losmapimod 7.5 mg BID
    Reporting group description
    		 Participants received oral losmapimod 7.5 milligrams (mg) BID according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.

    Primary: Number of participants with first occurrence of MACE through Week 12

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    End point title
    		 Number of participants with first occurrence of MACE through Week 12
    End point description
    Number of participants with first occurrence of major adverse cardiovascular events (MACE) through Week 12 including cardiovascular (CV) death, myocardial infarction (MI) or severe recurrent ischemia requiring urgent coronary artery revascularization (SRI-UR) are summarized. Death for which the clinical events committee (CEC) or investigator were unable to establish cause were analyzed as CV deaths. As losmapimod on MACE shown a statistically significant benefit compared to placebo, time to first occurrence analyzed by cox model with log-rank test. Hazard ratio and confidence interval (CI) were estimated using a cox proportional hazard regression model stratified by Baseline ST-segment elevation myocardial infarction (STEMI)/ non-ST-segment elevation myocardial infarction (NSTEMI) status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [1]
    1731 [2]
    Units: Participants
        First occurence of MACE
    123
    139
        CV Death
    34
    31
        MI
    74
    90
        SRI-UR
    15
    18
    Notes
    [1] - All Randomized (ITT) Population: all participants randomized to study treatment.
    [2] - All Randomized (ITT) Population: all participants randomized to study treatment.
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Losmapimod 7.5 mg BID v Placebo
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.238
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.47
    Notes
    [3] - Log rank test

    Secondary: Number of participants with first occurrence of MACE through Week 24

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    End point title
    		 Number of participants with first occurrence of MACE through Week 24
    End point description
    Number of participants with first occurrence of MACE through Week 24 including CV death, MI or SRI-UR are presented. Death for which the CEC or investigator were unable to establish cause were analyzed as CV deaths. Time to first occurrence analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [4]
    1731 [5]
    Units: Participants
        First occurrence of MACE
    162
    176
        CV Death
    45
    38
        MI
    98
    117
        SRI-UR
    19
    21
    Notes
    [4] - All Randomized (ITT) Population
    [5] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.329 [6]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.38
    Notes
    [6] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CV death or MI through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CV death or MI through to Week 12 and Week 24
    End point description
    Week 12 results are considered the principal secondary endpoint. Number of participants with first occurrence of the composite of CV death or MI through to Week 12 and Week 24 are summarized. Time to first occurrence analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [7]
    1731 [8]
    Units: Participants
        Week 12
    110
    122
        Week 24
    145
    156
    Notes
    [7] - All Randomized (ITT) Population
    [8] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Losmapimod 7.5 mg BID v Placebo
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.338 [9]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.47
    Notes
    [9] - Log rank test
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 24 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.41 [10]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.38
    Notes
    [10] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CV death, MI or hospitalization for heart failure (HF) through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CV death, MI or hospitalization for heart failure (HF) through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of CV death, MI or hospitalization for HF through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [11]
    1731 [12]
    Units: Participants
        Week 12
    131
    140
        Week 24
    169
    178
    Notes
    [11] - All Randomized (ITT) Population
    [12] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.472 [13]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.38
    Notes
    [13] - Log rank test

    Secondary: Number of participants with first occurrence of the expanded composite of arterial CV events defined as CV death, MI, SRI-UR or stroke through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the expanded composite of arterial CV events defined as CV death, MI, SRI-UR or stroke through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the expanded composite of arterial CV events defined as CV death, MI, SRI-UR or stroke through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [14]
    1731 [15]
    Units: Participants
        Week 12
    135
    151
        Week 24
    174
    190
    Notes
    [14] - All Randomized (ITT) Population
    [15] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.255 [16]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.44
    Notes
    [16] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of coronary events defined as CHD death, MI, SRI-UR or any unplanned coronary artery revascularization through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of coronary events defined as CHD death, MI, SRI-UR or any unplanned coronary artery revascularization through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of coronary events defined as coronary heart disease (CHD) death, MI, SRI-UR or any unplanned coronary artery revascularization through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [17]
    1731 [18]
    Units: Participants
        Week 12
    144
    152
        Week 24
    186
    194
    Notes
    [17] - All Randomized (ITT) Population
    [18] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.505 [19]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.36
    Notes
    [19] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CV death or hospitalization for HF through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CV death or hospitalization for HF through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of CV death or hospitalization for HF through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [20]
    1731 [21]
    Units: Participants
        Week 12
    72
    64
        Week 24
    94
    86
    Notes
    [20] - All Randomized (ITT) Population
    [21] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.536 [22]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.26
    Notes
    [22] - Log rank test
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 24 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6 [23]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.24
    Notes
    [23] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CV death, MI or stroke through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CV death, MI or stroke through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of CV death, MI or stroke through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [24]
    1731 [25]
    Units: Participants
        Week 12
    122
    134
        Week 24
    157
    170
    Notes
    [24] - All Randomized (ITT) Population
    [25] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Losmapimod 7.5 mg BID v Placebo
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.356 [26]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.43
    Notes
    [26] - Log rank test

    Secondary: Number of participants with first occurrence of the expanded composite of CV death, MI, SRI-UR, stroke or hospitalization for HF through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the expanded composite of CV death, MI, SRI-UR, stroke or hospitalization for HF through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the expanded composite of CV death, MI, SRI-UR, stroke or hospitalization for HF through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [27]
    1731 [28]
    Units: Participants
        Week 12
    155
    169
        Week 24
    197
    212
    Notes
    [27] - All Randomized (ITT) Population
    [28] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.329 [29]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.39
    Notes
    [29] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CHD death, MI or SRI-UR through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CHD death, MI or SRI-UR through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of CHD death, MI or SRI-UR through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [30]
    1731 [31]
    Units: Participants
        Week 12
    119
    133
        Week 24
    152
    167
    Notes
    [30] - All Randomized (ITT) Population
    [31] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.285 [32]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.47
    Notes
    [32] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CHD death or MI through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CHD death or MI through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of CHD death or MI through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [33]
    1731 [34]
    Units: Participants
        Week 12
    106
    116
        Week 24
    135
    147
    Notes
    [33] - All Randomized (ITT) Population
    [34] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.401 [35]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.46
    Notes
    [35] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of all-cause death, MI or SRI-UR through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of all-cause death, MI or SRI-UR through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of all-cause death, MI or SRI-UR through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [36]
    1731 [37]
    Units: Participants
        Week 12
    128
    142
        Week 24
    169
    185
    Notes
    [36] - All Randomized (ITT) Population
    [37] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.295 [38]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.44
    Notes
    [38] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of all-cause death or MI through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of all-cause death or MI through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of all-cause death or MI through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [39]
    1731 [40]
    Units: Participants
        Week 12
    115
    125
        Week 24
    152
    165
    Notes
    [39] - All Randomized (ITT) Population
    [40] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.412 [41]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.43
    Notes
    [41] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CV death, type I (spontaneous) MI or SRI-UR through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CV death, type I (spontaneous) MI or SRI-UR through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of CV death, type I (spontaneous) MI or SRI-UR through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [42]
    1731 [43]
    Units: Participants
        Week 12
    86
    94
        Week 24
    122
    127
    Notes
    [42] - All Randomized (ITT) Population
    [43] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.469 [44]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.49
    Notes
    [44] - Log rank test

    Secondary: Number of participants with first occurrence of the composite of CV death or type I (spontaneous) MI through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of the composite of CV death or type I (spontaneous) MI through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of the composite of CV death or type I (spontaneous) MI through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [45]
    1731 [46]
    Units: Participants
        Week 12
    73
    77
        Week 24
    104
    106
    Notes
    [45] - All Randomized (ITT) Population
    [46] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.664 [47]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.48
    Notes
    [47] - Log rank test

    Secondary: Number of participants with first occurrence of definite or probable stent thrombosis through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of definite or probable stent thrombosis through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of definite or probable stent thrombosis through to Week 12 and Week 24 are presented. Participants receiving stent prior to randomization or during the study prior to Week 12 were included. Only those participants available at the specified time points were analyzed (represented by n=X, X, in the category titles). Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [48]
    1731 [49]
    Units: Participants
        Week 12, n-1281, 1306
    19
    11
        Week 24, n=1758, 1731
    21
    12
    Notes
    [48] - All Randomized (ITT) Population
    [49] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13 [50]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 1.19
    Notes
    [50] - Log rank test

    Secondary: Number of participants re-hospitalized within 30 days of discharge

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    End point title
    		 Number of participants re-hospitalized within 30 days of discharge
    End point description
    Participants who had a death or re-hospitalization within 30 days of discharge, plus participants who were never discharged from the initial hospitalization were included. Odds ratio was estimated using a logistic regression model stratified by Baseline STEMI/NSTEMI status with treatment as the only covariate. An odds ratio <1 indicated a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Within up to 30 days of post discharge
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [51]
    1731 [52]
    Units: Participants
    210
    213
    Notes
    [51] - All Randomized (ITT) Population
    [52] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.744 [53]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.27
    Notes
    [53] - Wald chi-squared

    Secondary: Number of participants with all-cause mortality through to Week 12 and Week 24

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    End point title
    		 Number of participants with all-cause mortality through to Week 12 and Week 24
    End point description
    Number of participants with all-cause mortality through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [54]
    1731 [55]
    Units: Participants
        Week 12
    49
    39
        Week 24
    68
    57
    Notes
    [54] - All Randomized (ITT) Population
    [55] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Losmapimod 7.5 mg BID v Placebo
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.309 [56]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.22
    Notes
    [56] - Log rank test

    Secondary: Number of participants with CV death events through to Week 12 and Week 24

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    End point title
    		 Number of participants with CV death events through to Week 12 and Week 24
    End point description
    Number of participants with CV death events through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [57]
    1731 [58]
    Units: Participants
        Week 12
    44
    36
        Week 24
    59
    47
    Notes
    [57] - All Randomized (ITT) Population
    [58] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.398 [59]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.28
    Notes
    [59] - Log rank test
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 24 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.264 [60]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.18
    Notes
    [60] - Log rank test

    Secondary: Number of participants with CHD death events through to Week 12 and Week 24

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    End point title
    		 Number of participants with CHD death events through to Week 12 and Week 24
    End point description
    Number of participants with CHD death events through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [61]
    1731 [62]
    Units: Participants
        Week 12
    40
    30
        Week 24
    49
    37
    Notes
    [61] - All Randomized (ITT) Population
    [62] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.251 [63]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.22
    Notes
    [63] - Log rank test

    Secondary: Number of participants with first occurrence of myocardial infarction (fatal and non-fatal) events through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of myocardial infarction (fatal and non-fatal) events through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of myocardial infarction (fatal and non-fatal) events through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [64]
    1731 [65]
    Units: Participants
        Week 12
    75
    90
        Week 24
    99
    117
    Notes
    [64] - All Randomized (ITT) Population
    [65] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.182 [66]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.67
    Notes
    [66] - Log rank test
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 24 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.158 [67]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.58
    Notes
    [67] - Log rank test

    Secondary: Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [68]
    1731 [69]
    Units: Participants
        Week 12
    32
    42
        Week 24
    51
    62
    Notes
    [68] - All Randomized (ITT) Population
    [69] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.21 [70]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 2.12
    Notes
    [70] - Log rank st

    Secondary: Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [71]
    1731 [72]
    Units: Participants
        Week 12
    16
    18
        Week 24
    22
    22
    Notes
    [71] - All Randomized (ITT) Population
    [72] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.697 [73]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 2.24
    Notes
    [73] - Log rank test

    Secondary: Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [74]
    1731 [75]
    Units: Participants
        Week 12
    15
    14
        Week 24
    19
    18
    Notes
    [74] - All Randomized (ITT) Population
    [75] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.883 [76]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 1.96
    Notes
    [76] - Log rank test

    Secondary: Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [77]
    1731 [78]
    Units: Participants
        Week 12
    42
    35
        Week 24
    53
    49
    Notes
    [77] - All Randomized (ITT) Population
    [78] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.457 [79]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.32
    Notes
    [79] - Log rank test
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    week 24 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.736 [80]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.38
    Notes
    [80] - Log rank test

    Secondary: Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24

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    End point title
    		 Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24
    End point description
    Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24 are presented. Time to first occurrence at Week 12 analyzed by cox model with log-rank test. Hazard ratio and CI were estimated using a cox proportional hazard regression model stratified by Baseline STEMI/ NSTEMI status with treatment as the only covariate. A hazard ratio <1 indicates a lower risk with the treatment compared with placebo.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24
    End point values
    		 Placebo Losmapimod 7.5 mg BID
    Number of subjects analysed
    1758 [81]
    1731 [82]
    Units: Participants
        Week 12
    57
    62
        Week 24
    75
    87
    Notes
    [81] - All Randomized (ITT) Population
    [82] - All Randomized (ITT) Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 12 estimates
    Comparison groups
    Placebo v Losmapimod 7.5 mg BID
    Number of subjects included in analysis
    3489
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.581 [83]
    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
    		 1.59
    Notes
    [83] - Log rank test

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 26)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo BID according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.

    Reporting group title
    Losmapimod 7.5 mg BID
    Reporting group description
    		 Participants received oral losmapimod 7.5 mg BID according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks.

    Serious adverse events
    		 Placebo Losmapimod 7.5 mg BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    323 / 1752 (18.44%)
    363 / 1724 (21.06%)
         number of deaths (all causes)
    10
    13
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    3 / 1752 (0.17%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenocortical carcinoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone neoplasm
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Plasma cell myeloma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer metastatic
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Air embolism
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Artery dissection
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    4 / 1752 (0.23%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    5 / 1752 (0.29%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    3 / 1752 (0.17%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    6 / 1752 (0.34%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site haematoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    5 / 1752 (0.29%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 1752 (0.06%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Discomfort
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug intolerance
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    3 / 1752 (0.17%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    19 / 1752 (1.08%)
    15 / 1724 (0.87%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent restenosis
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersenstivity
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatism
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 1752 (0.06%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    4 / 1752 (0.23%)
    7 / 1724 (0.41%)
         occurrences causally related to treatment / all
    1 / 5
    1 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 1752 (0.11%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngospasm
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pharyngeal haematoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    6 / 1752 (0.34%)
    9 / 1724 (0.52%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 1752 (0.11%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary mass
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory depression
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheomalacia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety disorder due to a general medical condition
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder due to a general medical condition
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram change
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin abnormal
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laboratory test abnormal
         subjects affected / exposed
    3 / 1752 (0.17%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial necrosis marker increased
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin I increased
         subjects affected / exposed
    2 / 1752 (0.11%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    11 / 1752 (0.63%)
    9 / 1724 (0.52%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac procedure complication
         subjects affected / exposed
    1 / 1752 (0.06%)
    7 / 1724 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contrast media reaction
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary vascular graft occlusion
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to anastomose
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft loss
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic rupture
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Overdose
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    2 / 1752 (0.11%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural myocardial infarction
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postimplantation syndrome
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative renal failure
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    3 / 1752 (0.17%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 1752 (0.00%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative thoracic procedure complication
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Gastrointestinal arteriovenous malformation
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    7 / 1752 (0.40%)
    13 / 1724 (0.75%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    14 / 1752 (0.80%)
    24 / 1724 (1.39%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    24 / 1752 (1.37%)
    26 / 1724 (1.51%)
         occurrences causally related to treatment / all
    0 / 26
    0 / 27
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriospasm coronary
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    14 / 1752 (0.80%)
    19 / 1724 (1.10%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    4 / 1752 (0.23%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    4 / 1752 (0.23%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 1752 (0.00%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    3 / 1752 (0.17%)
    5 / 1724 (0.29%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    6 / 1752 (0.34%)
    10 / 1724 (0.58%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    5 / 1752 (0.29%)
    8 / 1724 (0.46%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    6 / 1752 (0.34%)
    5 / 1724 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 1752 (0.00%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery dissection
         subjects affected / exposed
    3 / 1752 (0.17%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery perforation
         subjects affected / exposed
    2 / 1752 (0.11%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery thrombosis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dressler's syndrome
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    3 / 1752 (0.17%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial rupture
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    2 / 1752 (0.11%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    3 / 1752 (0.17%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericarditis lupus
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postinfarction angina
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prinzmetal angina
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    4 / 1752 (0.23%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Torsade de pointes
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular flutter
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular dyssynchrony
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    5 / 1752 (0.29%)
    7 / 1724 (0.41%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachyarrhythmia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    5 / 1752 (0.29%)
    7 / 1724 (0.41%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Brain stem haemorrhage
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery disease
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    4 / 1752 (0.23%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    3 / 1752 (0.17%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Motor dysfunction
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychomotor hyperactivity
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Quadrantanopia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    5 / 1752 (0.29%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery stenosis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 1752 (0.06%)
    5 / 1724 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 1752 (0.06%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blindness
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic ischaemic neuropathy
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal mass
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 1752 (0.11%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Colitis ischaemic
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal perforation
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 1752 (0.00%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    3 / 1752 (0.17%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 1752 (0.17%)
    6 / 1724 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal pain
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal polyp haemorrhage
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal ulcer
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal ulcer haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    3 / 1752 (0.17%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic erosive gastritis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ulcer
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis ulcerative
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcerative gastritis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    2 / 1752 (0.11%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    4 / 1752 (0.23%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 1752 (0.06%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic ischaemia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic necrosis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity vasculitis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash generalised
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    9 / 1752 (0.51%)
    13 / 1724 (0.75%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder tamponade
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    3 / 1752 (0.17%)
    6 / 1724 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 1752 (0.11%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage urinary tract
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 1752 (0.06%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal haematoma
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urogenital haemorrhage
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Primary hyperaldosteronism
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back disorder
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    4 / 1752 (0.23%)
    14 / 1724 (0.81%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 1752 (0.00%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondritis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Acute hepatitis B
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    American trypanosomiasis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    3 / 1752 (0.17%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 1752 (0.00%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    2 / 1752 (0.11%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal infection
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    3 / 1752 (0.17%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 1752 (0.06%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 1752 (0.17%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    12 / 1752 (0.68%)
    16 / 1724 (0.93%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 18
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Post procedural cellulitis
         subjects affected / exposed
    1 / 1752 (0.06%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural pneumonia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Puncture site infection
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    4 / 1752 (0.23%)
    4 / 1724 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Septic shock
         subjects affected / exposed
    2 / 1752 (0.11%)
    2 / 1724 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Soft tissue infection
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 1752 (0.17%)
    5 / 1724 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    2 / 1752 (0.11%)
    3 / 1724 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Viral infection
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 1752 (0.06%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 1752 (0.06%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 1752 (0.11%)
    0 / 1724 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    0 / 1752 (0.00%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    2 / 1752 (0.11%)
    1 / 1724 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Placebo Losmapimod 7.5 mg BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    370 / 1752 (21.12%)
    376 / 1724 (21.81%)
    Investigations
    Troponin increased
         subjects affected / exposed
    39 / 1752 (2.23%)
    23 / 1724 (1.33%)
         occurrences all number
    39
    23
    Vascular disorders
    Hypertension
         subjects affected / exposed
    49 / 1752 (2.80%)
    33 / 1724 (1.91%)
         occurrences all number
    49
    34
    Hypotension
         subjects affected / exposed
    29 / 1752 (1.66%)
    36 / 1724 (2.09%)
         occurrences all number
    32
    36
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    32 / 1752 (1.83%)
    40 / 1724 (2.32%)
         occurrences all number
    33
    40
    Atrial fibrillation
         subjects affected / exposed
    65 / 1752 (3.71%)
    72 / 1724 (4.18%)
         occurrences all number
    66
    86
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    37 / 1752 (2.11%)
    39 / 1724 (2.26%)
         occurrences all number
    39
    41
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    35 / 1752 (2.00%)
    39 / 1724 (2.26%)
         occurrences all number
    36
    41
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    41 / 1752 (2.34%)
    44 / 1724 (2.55%)
         occurrences all number
    46
    48
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    41 / 1752 (2.34%)
    49 / 1724 (2.84%)
         occurrences all number
    41
    56
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    38 / 1752 (2.17%)
    47 / 1724 (2.73%)
         occurrences all number
    38
    47
    Dyspnoea
         subjects affected / exposed
    61 / 1752 (3.48%)
    48 / 1724 (2.78%)
         occurrences all number
    64
    48

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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
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