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    Clinical Trial Results:
    A Randomised, Double-blind, Placebo-controlled, Multi-center Sequential Phase 2b and Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 Administered for up to 48 Weeks in Participants with Heart Failure With Left Ventricular Ejection Fraction > 40%

    Summary
    EudraCT number
    		 2020-005844-47
    Trial protocol
    		 SE   SK   CZ   DK   BG   FR   HU   PL   NL   BE  
    Global end of trial date
    27 Mar 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Apr 2025
    First version publication date
    11 Apr 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D6580C00010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04986202
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    151 85, Södertälje, Sweden,
    Public contact
    Global Clinical Lead, AstraZeneca, +1 8772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +1 8772409479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 Jun 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Mar 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Mar 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy and safety of mitiperstat (previously known as AZD4831) in participants with heart failure (HF) with left ventricular ejection fraction (LVEF) > 40%.
    Protection of trial subjects
    Patients given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Jun 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Brazil: 42
    Country: Number of subjects enrolled
    Bulgaria: 96
    Country: Number of subjects enrolled
    Canada: 22
    Country: Number of subjects enrolled
    Czechia: 67
    Country: Number of subjects enrolled
    Denmark: 25
    Country: Number of subjects enrolled
    France: 19
    Country: Number of subjects enrolled
    Hungary: 56
    Country: Number of subjects enrolled
    Japan: 75
    Country: Number of subjects enrolled
    Netherlands: 14
    Country: Number of subjects enrolled
    Poland: 69
    Country: Number of subjects enrolled
    Russian Federation: 15
    Country: Number of subjects enrolled
    Slovakia: 76
    Country: Number of subjects enrolled
    Sweden: 37
    Country: Number of subjects enrolled
    Taiwan: 30
    Country: Number of subjects enrolled
    Türkiye: 4
    Country: Number of subjects enrolled
    United States: 50
    Worldwide total number of subjects
    709
    EEA total number of subjects
    468
    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)
    106
    From 65 to 84 years
    595
    85 years and over
    8

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 142 study centres in 18 countries randomised participants.

    Pre-assignment
    Screening details
    		 The discrepancy between the number of randomised participants and the number of participants in the full analysis set and the safety analysis set is because only randomized participants who have taken at least one dose of the investigational product (IP) were included in the analysis sets.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 AZD4831 2.5 mg
    Arm description
    		 Once-daily oral dosing of AZD4831 2.5 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    AZD4831
    Investigational medicinal product code
    Other name
    Mitiperstat
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2.5 mg once daily

    Arm title
    		 AZD4831 5 mg
    Arm description
    		 Once-daily oral dosing of AZD4831 5 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    AZD4831
    Investigational medicinal product code
    Other name
    Mitiperstat
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg once daily

    Arm title
    		 Placebo
    Arm description
    		 Once-daily oral dosing of placebo
    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
    Once daily

    Number of subjects in period 1
    		AZD4831 2.5 mg AZD4831 5 mg Placebo
    Started
    234
    240
    235
    Completed
    218
    234
    220
    Not completed
    16
    6
    15
         Adverse event, serious fatal
    10
    3
    10
         Physician decision
    2
    1
    2
         Consent withdrawn by subject
    4
    2
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    AZD4831 2.5 mg
    Reporting group description
    		 Once-daily oral dosing of AZD4831 2.5 mg

    Reporting group title
    AZD4831 5 mg
    Reporting group description
    		 Once-daily oral dosing of AZD4831 5 mg

    Reporting group title
    Placebo
    Reporting group description
    		 Once-daily oral dosing of placebo

    Reporting group values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo Total
    Number of subjects
    		 234 240 235 709
    Age Categorical
    Units: Participants
        < 65 Years
    		 34 42 30 106
        65 - 75 Years
    		 120 108 115 343
        > 75 Years
    		 80 90 90 260
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 72.5 ( 7.3 ) 72.1 ( 7.1 ) 72.5 ( 7.8 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 107 119 96 322
        Male
    		 127 121 139 387
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 16 14 21 51
        Not Hispanic or Latino
    		 218 226 214 658
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 35 36 36 107
        Black or African American
    		 5 10 6 21
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        White
    		 193 194 192 579
        Other
    		 1 0 1 2
        Not Reported
    		 0 0 0 0
    Region of Enrollment
    Units: Subjects
        Australia
    		 1 1 1 3
        Belgium
    		 3 3 3 9
        Brazil
    		 13 14 15 42
        Bulgaria
    		 33 32 31 96
        Canada
    		 8 8 6 22
        Czech Republic
    		 23 22 22 67
        Denmark
    		 8 9 8 25
        France
    		 6 7 6 19
        Hungary
    		 18 19 19 56
        Japan
    		 25 25 25 75
        Netherlands
    		 4 5 5 14
        Poland
    		 22 23 24 69
        Russian Federation
    		 5 5 5 15
        Slovakia
    		 25 26 25 76
        Sweden
    		 12 12 13 37
        Taiwan
    		 10 10 10 30
        Turkey
    		 1 2 1 4
        United States of America
    		 17 17 16 50

    End points

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    End points reporting groups
    Reporting group title
    AZD4831 2.5 mg
    Reporting group description
    		 Once-daily oral dosing of AZD4831 2.5 mg

    Reporting group title
    AZD4831 5 mg
    Reporting group description
    		 Once-daily oral dosing of AZD4831 5 mg

    Reporting group title
    Placebo
    Reporting group description
    		 Once-daily oral dosing of placebo

    Primary: Kansas City Cardiomyopathy Questionnaire -Total Symptom Score 16 weeks

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    End point title
    		 Kansas City Cardiomyopathy Questionnaire -Total Symptom Score 16 weeks
    End point description
    Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 16 weeks compared with placebo Part A. The score ranges from 0 to 100, where a higher score represents a better patient outcome
    End point type
    Primary
    End point timeframe
    Baseline - 16 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    211
    221
    220
    Units: Points
        least squares mean (confidence interval 95%)
    10.70 (8.58 to 12.82)
    9.81 (7.73 to 11.90)
    11.62 (9.54 to 13.71)
    Statistical analysis title
    		 Difference in least-squares means
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    441
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.221 [1]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.71
         upper limit
    		 1.09
    Notes
    [1] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.537 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.86
         upper limit
    		 2.02
    Notes
    [2] - Two-sided test.

    Primary: Six Minute Walk Distance 16 weeks

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    End point title
    		 Six Minute Walk Distance 16 weeks
    End point description
    Six Minute Walk Distance change from baseline at 16 weeks compared with placebo Part A
    End point type
    Primary
    End point timeframe
    Baseline - 16 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    210
    223
    223
    Units: Meters
        least squares mean (confidence interval 95%)
    15.3 (9.4 to 21.2)
    18.2 (12.4 to 23.9)
    12.9 (7.2 to 18.7)
    Statistical analysis title
    		 Difference in least-squares means
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    446
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.195 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 13.3
    Notes
    [3] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    433
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.559 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 10.5
    Notes
    [4] - Two-sided test.

    Secondary: Kansas City Cardiomyopathy Questionnaire-Total Symptom Score

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    End point title
    		 Kansas City Cardiomyopathy Questionnaire-Total Symptom Score
    End point description
    Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 24 and 48 weeks compared with placebo Part A. The score ranges from 0 to 100, where a higher score represents a better patient outcome.
    End point type
    Secondary
    End point timeframe
    Baseline - 24 and 48 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    208 [5]
    225 [6]
    210 [7]
    Units: Points
    least squares mean (confidence interval 95%)
        Change from baseline at 24 weeks
    11.13 (8.94 to 13.32)
    11.92 (9.80 to 14.03)
    12.78 (10.59 to 14.97)
        Change from baseline at 48 weeks
    12.78 (10.25 to 15.30)
    11.98 (9.50 to 14.46)
    13.03 (10.47 to 15.58)
    Notes
    [5] - For 48 weeks, the number of subjects analyzed is 194.
    [6] - For 48 weeks, the number of subjects analyzed is 204.
    [7] - For 48 weeks, the number of subjects analyzed is 193.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.289 [8]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.71
         upper limit
    		 1.41
    Notes
    [8] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    435
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.558 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.55
         upper limit
    		 2.46
    Notes
    [9] - For 48 weeks, the number of subjects in the analysis is 397
    [10] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.89 [12]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.8
         upper limit
    		 3.3
    Notes
    [11] - For 48 weeks, the number of subjects in the analysis is 387.
    [12] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares mean
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    435
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.571 [13]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.86
         upper limit
    		 2.13
    Notes
    [13] - Two-sided test.

    Secondary: Six Minute Walk Distance

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    End point title
    		 Six Minute Walk Distance
    End point description
    Six Minute Walk Distance change from baseline at 24 and 48 weeks compared with placebo Part A
    End point type
    Secondary
    End point timeframe
    Baseline - 24 and 48 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    202 [14]
    222 [15]
    211 [16]
    Units: Meters
    least squares mean (confidence interval 95%)
        Change from baseline at 24 weeks
    13.5 (7.1 to 19.8)
    18.5 (12.4 to 24.6)
    15.7 (9.4 to 22.0)
        Change from baseline at 48 weeks
    19.2 (11.9 to 26.4)
    15.7 (8.6 to 22.7)
    13.5 (6.3 to 20.6)
    Notes
    [14] - For 48 weeks, the number of subjects analyzed is 190.
    [15] - For 48 weeks, the number of subjects analyzed is 205.
    [16] - For 48 weeks, the number of subjects analyzed is 201.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    413
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.619 [17]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.1
         upper limit
    		 6.6
    Notes
    [17] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    413
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 = 0.267 [19]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 15.8
    Notes
    [18] - For 48 weeks, the number of subjects in the analysis is 391
    [19] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    433
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 = 0.657 [21]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.6
         upper limit
    		 12.1
    Notes
    [20] - For 48 weeks, the number of subjects in the analysis is 406
    [21] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    433
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.522 [22]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.8
         upper limit
    		 11.4
    Notes
    [22] - Two-sided test.

    Secondary: N-terminal pro-brain natriuretic peptide (NT-proBNP)

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    End point title
    		 N-terminal pro-brain natriuretic peptide (NT-proBNP)
    End point description
    NT-proBNP change from baseline at 16, 24, and 48 weeks compared with placebo Part A
    End point type
    Secondary
    End point timeframe
    Baseline - 16, 24 and 48 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    212 [23]
    223 [24]
    220 [25]
    Units: ng/L
    geometric mean (confidence interval 95%)
        NT-proBNP change from baseline at 16 weeks
    1.00 (0.93 to 1.08)
    0.96 (0.90 to 1.03)
    1.05 (0.98 to 1.13)
        NT-proBNP change from baseline at 24 weeks
    1.00 (0.92 to 1.07)
    1.00 (0.93 to 1.08)
    0.99 (0.92 to 1.07)
        NT-proBNP change from baseline at 48 weeks
    1.02 (0.94 to 1.11)
    1.00 (0.93 to 1.09)
    1.08 (0.99 to 1.17)
    Notes
    [23] - For 24 and 48 weeks, the numbers of subjects analyzed are 210 and 195.
    [24] - For 24 and 48 weeks, the numbers of subjects analyzed are 228 and 212.
    [25] - For 24 and 48 weeks, the numbers of subjects analyzed are 218 and 201.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    NT-proBNP change from baseline at 16 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    432
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.312 [26]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.05
    Notes
    [26] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    NT-proBNP change from baseline at 16 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.07 [27]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.01
    Notes
    [27] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    NT-proBNP change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    432
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    P-value
    		 = 0.911 [29]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.12
    Notes
    [28] - For 24 weeks, the number of subjects in the analysis is 428
    [29] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    NT-proBNP change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    P-value
    		 = 0.837 [31]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.12
    Notes
    [30] - For 24 weeks, the number of subjects in the analysis is 446
    [31] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    NT-proBNP change from baseline at 48 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    432
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    P-value
    		 = 0.37 [33]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.07
    Notes
    [32] - For 48 weeks, the number of subjects in the analysis is 396
    [33] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    NT-proBNP change from baseline at 48 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [34]
    P-value
    		 = 0.205 [35]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.04
    Notes
    [34] - For 48 weeks, the number of subjects in the analysis is 413
    [35] - Two-sided test.

    Secondary: Left ventricular global longitudinal strain (LV-GLS)

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    End point title
    		 Left ventricular global longitudinal strain (LV-GLS)
    End point description
    LV-GLS change from baseline at 16 and 24 weeks compared with placebo Part A
    End point type
    Secondary
    End point timeframe
    Baseline - 16 and 24 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    109 [36]
    121 [37]
    117 [38]
    Units: Percentage (%)
    least squares mean (confidence interval 95%)
        LV-GLS change from baseline at 16 weeks
    0.1 (-0.5 to 0.6)
    -0.5 (-1.0 to 0.0)
    -0.4 (-1.0 to 0.1)
        LV-GLS change from baseline at 24 weeks
    -0.6 (-1.1 to 0.0)
    -0.9 (-1.4 to -0.4)
    -1.0 (-1.5 to -0.4)
    Notes
    [36] - For 24 weeks, the number of subjects analyzed is 114.
    [37] - For 24 weeks, the number of subjects analyzed is 132.
    [38] - For 24 weeks, the number of subjects analyzed is 121.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    226
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.183 [39]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 1.2
    Notes
    [39] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    226
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [40]
    P-value
    		 = 0.316 [41]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 1.1
    Notes
    [40] - For 24 weeks, the number of subjects in the analysis is 235
    [41] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    238
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [42]
    P-value
    		 = 0.934 [43]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.8
    Notes
    [42] - For 24 weeks, the number of subjects in the analysis is 253
    [43] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    238
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.898 [44]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.7
    Notes
    [44] - Two-sided test.

    Secondary: Left atrial volume index (LAVI)

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    End point title
    		 Left atrial volume index (LAVI)
    End point description
    LAVI change from baseline at 16 and 24 weeks compared with placebo Part A
    End point type
    Secondary
    End point timeframe
    Baseline - 16 and 24 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    184 [45]
    196 [46]
    184 [47]
    Units: mL/m2
    least squares mean (confidence interval 95%)
        LAVI change from baseline at 16 weeks
    -0.940 (-2.373 to 0.493)
    -1.894 (-3.286 to -0.502)
    -1.300 (-2.743 to 0.144)
        LAVI change from baseline at 24 weeks
    1.096 (-0.626 to 2.818)
    -0.376 (-1.986 to 1.235)
    0.439 (-1.236 to 2.114)
    Notes
    [45] - For 24 weeks, the number of subjects analyzed is 176.
    [46] - For 24 weeks, the number of subjects analyzed is 201.
    [47] - For 24 weeks, the number of subjects analyzed is 189.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.725 [48]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.647
         upper limit
    		 2.366
    Notes
    [48] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    380
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.555 [49]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.594
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.571
         upper limit
    		 1.382
    Notes
    [49] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [50]
    P-value
    		 = 0.586 [51]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.657
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.71
         upper limit
    		 3.025
    Notes
    [50] - For 24 weeks, the number of subjects in the analysis is 365
    [51] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    380
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [52]
    P-value
    		 = 0.486 [53]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.815
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.108
         upper limit
    		 1.478
    Notes
    [52] - For 24 weeks, the number of subjects in the analysis is 390
    [53] - Two-sided test.

    Secondary: Left ventricular mass index (LVMI)

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    End point title
    		 Left ventricular mass index (LVMI)
    End point description
    LVMI change from baseline at 16 and 24 weeks compared with placebo Part A
    End point type
    Secondary
    End point timeframe
    Baseline - 16 and 24 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    200 [54]
    208 [55]
    204 [56]
    Units: g/m2
    least squares mean (confidence interval 95%)
        LVMI change from baseline at 16 weeks
    1.3 (-1.6 to 4.2)
    -0.9 (-3.8 to 1.9)
    1.4 (-1.5 to 4.2)
        LVMI change from baseline at 24 weeks
    9.8 (6.0 to 13.5)
    8.3 (4.6 to 11.9)
    9.4 (5.6 to 13.1)
    Notes
    [54] - For 24 weeks, the number of subjects analyzed is 197.
    [55] - For 24 weeks, the number of subjects analyzed is 213.
    [56] - For 24 weeks, the number of subjects analyzed is 202.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.968 [57]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.1
         upper limit
    		 3.9
    Notes
    [57] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    412
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.251 [58]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.3
         upper limit
    		 1.6
    Notes
    [58] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [59]
    P-value
    		 = 0.872 [60]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 5.7
    Notes
    [59] - For 24 weeks, the number of subjects in the analysis is 399
    [60] - Two-sided test.
    Statistical analysis title
    		 Difference in least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    412
    Analysis specification
    Pre-specified
    Analysis type
    		 [61]
    P-value
    		 = 0.682 [62]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.2
         upper limit
    		 4.1
    Notes
    [61] - For 24 weeks, the number of subjects in the analysis is 415
    [62] - Two-sided test.

    Secondary: Pharmacokinetics (AZD4831 plasma exposure)

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    End point title
    		 Pharmacokinetics (AZD4831 plasma exposure)
    End point description
    Plasma concentrations of AZD4831 summarised by timepoint and dose level Part A
    End point type
    Secondary
    End point timeframe
    Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks, 48 weeks, 52 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    231 [63]
    238 [64]
    0 [65]
    Units: nmol/L
    geometric mean (geometric coefficient of variation)
        Baseline (pre-dose)
    1.02 ( 19.57 )
    1.01 ( 9.38 )
    ( )
        4 weeks (pre-dose)
    14.45 ( 99.26 )
    26.44 ( 141.88 )
    ( )
        12 weeks (pre-dose)
    13.51 ( 130.33 )
    25.45 ( 161.09 )
    ( )
        16 weeks (pre-dose)
    13.59 ( 126.71 )
    25.31 ( 159.79 )
    ( )
        24 weeks (pre-dose)
    12.87 ( 146.45 )
    23.08 ( 199.18 )
    ( )
        48 weeks (pre-dose)
    10.36 ( 188.55 )
    21.18 ( 229.28 )
    ( )
        52 weeks (pre-dose)
    1.14 ( 49.22 )
    1.27 ( 74.56 )
    ( )
    Notes
    [63] - The number of subjects analyzed is for baseline and varies for other timepoints.
    [64] - The number of subjects analyzed is for baseline and varies for other timepoints.
    [65] - No samples from participants on placebo were analysed.
    No statistical analyses for this end point

    Secondary: High sensitivity CRP (hsCRP)

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    End point title
    		 High sensitivity CRP (hsCRP)
    End point description
    hsCRP change from baseline at 16, 24, and 48 weeks compared with placebo Part A
    End point type
    Secondary
    End point timeframe
    Baseline - 16, 24 and 48 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    210 [66]
    224 [67]
    218 [68]
    Units: mg/dL
    geometric mean (confidence interval 95%)
        hsCRP change from baseline at 16 weeks
    0.940 (0.824 to 1.073)
    1.105 (0.971 to 1.257)
    0.914 (0.802 to 1.041)
        hsCRP change from baseline at 24 weeks
    1.029 (0.907 to 1.168)
    1.101 (0.976 to 1.243)
    0.926 (0.816 to 1.051)
        hsCRP change from baseline at 48 weeks
    1.120 (0.973 to 1.288)
    1.127 (0.985 to 1.290)
    0.972 (0.845 to 1.119)
    Notes
    [66] - For 24 and 48 weeks, the numbers of subjects analyzed are 209 and 196.
    [67] - For 24 and 48 weeks, the numbers of subjects analyzed are 229 and 215.
    [68] - For 24 and 48 weeks, the numbers of subjects analyzed are 210 and 197.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.76 [69]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.029
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.857
         upper limit
    		 1.236
    Notes
    [69] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    442
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [70]
    P-value
    		 = 0.131 [71]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.159
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.957
         upper limit
    		 1.404
    Notes
    [70] - For 48 weeks, the number of subjects in the analysis is 412
    [71] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    442
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [72]
    P-value
    		 = 0.049 [73]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.001
         upper limit
    		 1.414
    Notes
    [72] - For 24 weeks, the number of subjects in the analysis is 439
    [73] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [74]
    P-value
    		 = 0.158 [75]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.151
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.946
         upper limit
    		 1.401
    Notes
    [74] - For 48 weeks, the number of subjects in the analysis is 393
    [75] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    442
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.039 [76]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.209
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.01
         upper limit
    		 1.448
    Notes
    [76] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [77]
    P-value
    		 = 0.241 [78]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.111
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.931
         upper limit
    		 1.326
    Notes
    [77] - For 24 weeks, the number of subjects in the analysis is 419
    [78] - Two-sided test.

    Secondary: Interleukin 6 (IL-6)

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    End point title
    		 Interleukin 6 (IL-6)
    End point description
    IL-6 change from baseline at 16, 24, and 48 weeks compared with placebo Part A
    End point type
    Secondary
    End point timeframe
    Baseline - 16, 24 and 48 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    190 [79]
    201 [80]
    199 [81]
    Units: ng/L
    geometric mean (confidence interval 95%)
        IL-6 change from baseline at 16 weeks
    1.1326 (1.0261 to 1.2502)
    1.0258 (0.9316 to 1.1295)
    1.1202 (1.0170 to 1.2339)
        IL-6 change from baseline at 24 weeks
    1.0918 (0.9934 to 1.2000)
    1.0700 (0.9777 to 1.1711)
    0.9869 (0.8975 to 1.0852)
        IL-6 change from baseline at 48 weeks
    1.3328 (1.2134 to 1.4639)
    1.3094 (1.1972 to 1.4321)
    1.2698 (1.1574 to 1.3931)
    Notes
    [79] - For 24 and 48 weeks, the numbers of subjects analyzed are 189 and 170.
    [80] - For 24 and 48 weeks, the numbers of subjects analyzed are 209 and 189.
    [81] - For 24 and 48 weeks, the numbers of subjects analyzed are 188 and 177.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    389
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.874 [82]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.0111
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8819
         upper limit
    		 1.1592
    Notes
    [82] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 16 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2 [83]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.9157
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8002
         upper limit
    		 1.0479
    Notes
    [83] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 [84]
    P-value
    		 = 0.636 [85]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.0312
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.908
         upper limit
    		 1.1711
    Notes
    [84] - For 48 weeks, the number of subjects in the analysis is 366
    [85] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 5 mg v Placebo
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [86]
    P-value
    		 = 0.22 [87]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.0842
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9527
         upper limit
    		 1.2339
    Notes
    [86] - For 24 weeks, the number of subjects in the analysis is 397
    [87] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 48 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    389
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [88]
    P-value
    		 = 0.467 [89]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.0496
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9211
         upper limit
    		 1.196
    Notes
    [88] - For 48 weeks, the number of subjects in the analysis is 347
    [89] - Two-sided test.
    Statistical analysis title
    		 Difference in geometric least-squares means
    Statistical analysis description
    Change from baseline at 24 weeks
    Comparison groups
    AZD4831 2.5 mg v Placebo
    Number of subjects included in analysis
    389
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [90]
    P-value
    		 = 0.135 [91]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.1063
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.969
         upper limit
    		 1.2631
    Notes
    [90] - For 24 weeks, the number of subjects in the analysis is 377
    [91] - Two-sided test.

    Other pre-specified: Adverse Events

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    End point title
    		 Adverse Events
    End point description
    Number of participants with Adverse Events Part A
    End point type
    Other pre-specified
    End point timeframe
    Baseline - 52 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    234
    240
    235
    Units: Participants
    173
    180
    173
    No statistical analyses for this end point

    Other pre-specified: Vital Signs

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    End point title
    		 Vital Signs
    End point description
    Number of participants with treatment emergent vital sign abnormalities Part A
    End point type
    Other pre-specified
    End point timeframe
    Baseline - 52 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    233 [92]
    240 [93]
    235 [94]
    Units: Participants
        DBP>=90 & increase fr baseline>=10 (mmHg)
    62
    60
    68
        DBP<60 & decrease fr baseline>=10 (mmHg)
    32
    42
    33
        Pulse>=100 & increase fr baseline>=20 (beats/min)
    15
    17
    11
        Pulse <50 & decrease fr baseline>=20 (beats/min)
    2
    6
    8
        SBP>=140 & increase fr baseline>=20 (mmHg)
    71
    84
    67
        SBP<90 & decrease fr baseline>=20 (mmHg)
    5
    3
    3
    Notes
    [92] - Number of subjects with a baseline value and at least one post-baseline value.
    [93] - Number of subjects with a baseline value and at least one post-baseline value.
    [94] - Number of subjects with a baseline value and at least one post-baseline value.
    No statistical analyses for this end point

    Other pre-specified: Clinical Laboratory

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    End point title
    		 Clinical Laboratory
    End point description
    Number of participants with outliers for clinical laboratory measurements Part A
    End point type
    Other pre-specified
    End point timeframe
    Baseline - 52 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    227 [95]
    238 [96]
    232 [97]
    Units: Participants
        Eosinophils >= 0.7 (10^9/L)
    4
    4
    8
        Eosinophils >= 1.5 (10^9/L)
    0
    0
    0
        Hemoglobin < 100 (10^9/L)
    9
    11
    6
        Hemoglobin < 8 (10^9/L)
    1
    1
    0
        Neutrophil count < 1.5 (10^9/L)
    2
    7
    3
        Neutrophil count < 1.0 (10^9/L)
    0
    1
    0
        Leukocytes < 3.0 (10^9/L)
    3
    5
    6
        Leukocytes < 2.0 (10^9/L)
    0
    1
    0
        ALP > 1.5x ULN
    9
    8
    13
        ALP > 3x ULN
    0
    0
    1
        ALT > 3x ULN
    5
    2
    3
        ALT > 5x ULN
    2
    0
    1
        ALT > 10x ULN
    0
    0
    0
        AST > 3x ULN
    3
    3
    4
        AST > 5x ULN
    1
    0
    0
        AST > 10x ULN
    0
    0
    0
        Creatinine >= 1.5x baseline creatinine
    15
    10
    14
        Creatinine >= 2x baseline creatinine
    3
    0
    2
        TB > 1.5x ULN
    6
    1
    12
        TB > 2x ULN
    1
    1
    2
        AST or ALT > 3x ULN
    6
    3
    4
        AST or ALT > 3x ULN and TB > 2x ULN
    0
    0
    1
        TSH >=6 (mIU/L)
    19
    25
    18
        TSH >=10 (mIU/L)
    12
    6
    3
        TSH > 6 and free T4 < LLN (mIU/L)
    2
    1
    0
        TSH >= 10 and free T4 < LLN (mIU/L)
    2
    0
    0
    Notes
    [95] - Number of subjects with a baseline value and at least one post-baseline value.
    [96] - Number of subjects with a baseline value and at least one post-baseline value. Chemistry: 239
    [97] - Number of subjects with a baseline value and at least one post-baseline value.
    No statistical analyses for this end point

    Other pre-specified: Electrocardiogram (ECG)

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    End point title
    		 Electrocardiogram (ECG)
    End point description
    Number of Participants With Abnormal ECG Last On-Study Value Part A
    End point type
    Other pre-specified
    End point timeframe
    Baseline - 52 weeks
    End point values
    		 AZD4831 2.5 mg AZD4831 5 mg Placebo
    Number of subjects analysed
    226 [98]
    239 [99]
    232 [100]
    Units: Participants
        Normal; Normal at baseline
    43
    52
    49
        Abn, not clin sig; Normal at baseline
    17
    19
    14
        Abn, clin sig last on-study; Normal at baseline
    2
    0
    1
        Normal; Abn, not clin sig at baseline
    8
    14
    7
        Abn, not clin sig; Abn, not clin sig at baseline
    132
    135
    137
        Abn, clin sig; Abn, not clin sig at baseline
    5
    2
    4
        Normal; Abn, clin sig at baseline
    0
    0
    1
        Abn, not clin sig; Abn clin sig at baseline
    6
    7
    12
        Abn, clin sig; Abn, clin sig at baseline
    13
    10
    7
    Notes
    [98] - Number of subjects with a baseline value and at least one post-baseline value.
    [99] - Number of subjects with a baseline value and at least one post-baseline value.
    [100] - Number of subjects with a baseline value and at least one post-baseline value.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until last study visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    AZD4831 2.5mg
    Reporting group description
    		 -

    Reporting group title
    AZD4831 5mg
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo AZD4831 2.5mg AZD4831 5mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    56 / 235 (23.83%)
    60 / 234 (25.64%)
    57 / 240 (23.75%)
         number of deaths (all causes)
    10
    10
    3
         number of deaths resulting from adverse events
    10
    10
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Carcinoid tumour pulmonary
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colorectal adenoma
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lip squamous cell carcinoma
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma in situ
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salivary gland neoplasm
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Brachiocephalic arteriosclerosis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 234 (0.43%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iliac artery embolism
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular insufficiency
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Social circumstances
    Alcohol use
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    2 / 240 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood sodium decreased
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chemical burn
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 234 (0.85%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute left ventricular failure
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 235 (0.43%)
    4 / 234 (1.71%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 235 (0.85%)
    3 / 234 (1.28%)
    3 / 240 (1.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 235 (1.28%)
    2 / 234 (0.85%)
    5 / 240 (2.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 234 (0.43%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    13 / 235 (5.53%)
    10 / 234 (4.27%)
    13 / 240 (5.42%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 11
    0 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis constrictive
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 234 (0.85%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cerebral infarction
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Optic neuritis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 234 (1.28%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    2 / 240 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Immune thrombocytopenia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normocytic anaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vestibular disorder
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Blindness
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scleritis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Duodenal ulcer perforation
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal strangulated hernia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 234 (0.85%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumoperitoneum
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema multiforme
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    2 / 240 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    2 / 240 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 234 (0.85%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 235 (0.00%)
    3 / 234 (1.28%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 234 (0.85%)
    2 / 240 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis orbital
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Citrobacter bacteraemia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 234 (0.85%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 234 (0.85%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella urinary tract infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia moraxella
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    Septic shock
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 234 (0.43%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 234 (0.85%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection bacterial
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 234 (0.00%)
    1 / 240 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 234 (0.00%)
    0 / 240 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo AZD4831 2.5mg AZD4831 5mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    45 / 235 (19.15%)
    49 / 234 (20.94%)
    44 / 240 (18.33%)
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    14 / 235 (5.96%)
    11 / 234 (4.70%)
    11 / 240 (4.58%)
         occurrences all number
    14
    14
    13
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    12 / 235 (5.11%)
    18 / 234 (7.69%)
    10 / 240 (4.17%)
         occurrences all number
    15
    21
    12
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    15 / 235 (6.38%)
    9 / 234 (3.85%)
    13 / 240 (5.42%)
         occurrences all number
    21
    12
    15
    COVID-19
         subjects affected / exposed
    15 / 235 (6.38%)
    16 / 234 (6.84%)
    18 / 240 (7.50%)
         occurrences all number
    15
    16
    18

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 May 2021
    Amendment 1
    01 Nov 2021
    Amendment 2
    09 Feb 2022
    Amendment 3
    23 Sep 2022
    Amendment 4

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

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

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