Study to Evaluate the Efficacy and Safety of AZD4831 in Participants with Heart Failure with Left Ventricular Ejection Fraction > 40% - ENDEAVOR

Study identifier:D6580C00010

ClinicalTrials.gov identifier:NCT04986202

EudraCT identifier:2020-005844-47

CTIS identifier:N/A

Study Complete

Official Title

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%

Medical condition

Heart Failure with preserved Ejection Fraction

Phase

Phase 2/3

Healthy volunteers

Study drug

AZD4831

Sex

All

Actual Enrollment

711

Study type

Interventional

Age

40 Years - 85 Years

Date

Study Start Date: 30 Jun 2021

Primary Completion Date: 27 Mar 2024

Study Completion Date: 27 Mar 2024

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2025 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

Part A
1. ≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
2. Documented stable symptomatic HF (New York Heart Association Class II-IV) for at least 1 month at Screening (Visit 1) (transient HF in the setting of an MI does not qualify), with a medical history of typical symptoms of HF and receiving optimal therapy for HF as determined by the health-care physician.
3. LVEF > 40% at Screening (Visit 1). All participants will undergo a local echocardiogram at the Screening (Visit 1) with central reading to confirm the LVEF > 40% eligibility criteria before randomisation.
4. 6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 3). Difference in 6MWD between Screening and Randomisation must be < 50 meters.
5. KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 3)
6.NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤30 kg/m2.
NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2.
The ECG performed at Screening should be used for heart rhythm evaluation.
7.At least one of the following:
(a) Structural heart disease, ie, LA enlargement and/or left ventricular hypertrophy at the echocardiogram performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width (diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34 mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or LVMI > 95 g/m2 in women and > 115 g/m2 in men.
(b) Spectral tissue Doppler echocardiography - E/e’ ratio (average of septal and lateral) ≥ 13 at rest at the echocardiogram performed at Screening (Visit 1).
(c) Indirectly estimated elevation of PASP by TRmax velocity > 2.8 m/s (280 cm/s) (PASP > 35 mmHg) at the echocardiogram performed at Screening (Visit 1) OR directly measured pulmonary capillary wedge pressure > 15 mmHg at rest within the past 12 months or > 25 mmHg at exercise documented by right heart catheterisation within 12 months prior to Screening (Visit 1).
(d) HF decompensation within 6 months before Randomisation (Visit 3), defined as hospitalisation for HF or IV diuretic treatment for HF during an urgent, unscheduled visit without hospitalisation.
8.Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
9.Male or female of non-childbearing potential.
Part B
1. Participant must be ≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
2. Documented diagnosis of symptomatic HF (NYHA class II-IV) at Screening (Visit 1), and a medical history of typical symptoms/signs of heart failure ≥ 6 weeks before Screening (Visit 1), and receiving optimal therapy for HF as determined by the health-care physician, with at least intermittent need for diuretic treatment.
3. LVEF >40% and evidence of structural heart disease (ie, left ventricular hypertrophy or
left atrial enlargement [defined by at least one of the following:LA enlargement and/or left ventricular hypertrophy at the echocardiogram
performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width
(diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34
mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or
LVMI > 95 g/m2 in women and > 115 g/m2 in men.]) documented by the most recent echocardiogram, or cardiac
magnetic resonance imaging within the last 12 months prior to Screening (Visit 1). If no
echocardiogram is available, it can be performed at Screening (Visit 1).
4. 6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 2). Difference in 6MWD between Screening and Randomisation must be < 50 meters
5. KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 2).
6. NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤ 30 kg/m2. NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2. The ECG performed at Screening should be used for heart rhythm evaluation
7. Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
8. Male or female of non-childbearing potential.

Exclusion Criteria

Part A
1 eGFR < 30 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration formula) at Screening (Visit 1).
2. Systolic blood pressure < 90 mmHg or ≥ 160 mmHg if not on treatment with ≥ 3 blood pressure lowering medications or ≥ 180 mmHg irrespective of treatments at Randomisation
3. Heart rate > 110 bpm or < 50 bpm at Randomisation
4. Life expectancy < 3 years due to other reasons than cardiovascular disease.
5. History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).
6. Presence of any disease or condition rather than HF constituting the main reason for limiting the ability to exercise/reduced exercise capacity.
7. Current decompensated HF and/or NT-proBNP > 5000 pg/mL at Screening (Visit 1)
8. Documented history of ejection fraction ≤ 40%.i.e. HF with recovered ejection fraction. Transient ejection fraction decrease e.g. in the setting of an MI does not apply
9. Any planned cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).
10. Any cardiac event (eg, myocardial infarction, unstable angina), coronary revascularisation (percutaneous coronary intervention or coronary artery bypass grafting), ablation of atrial fibrillation/flutter, valve repair/replacement, implantation of a cardiac resynchronisation therapy device within 12 weeks prior to Screening (Visit 1) or between Screening and Randomisation. Patients who underwent a successful atrial fibrillation/flutter cardioversion, can be enrolled in the study after 4 weeks.
14. Hb < 110 g/L (male) and < 100 g/L (female) or iron-deficiency with/without anaemia requiring ongoing or planned IV iron treatment.
15. Participants with hyperthyroidism, uncontrolled hypothyroidism (including but not limited to TSH ≥10 mIU/mL), or any clinically significant thyroid disease as judged by the investigator.
18. ALT or AST ≥ 2 × ULN at Screening (Visit 1).
19. Pulmonary arterial hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening (Visit 1).
20. Any active infection requiring oral, intravenous or intramuscular treatment at Screening (Visit 1) and/or at Randomisation.
23 Any signs or confirmation of COVID-19 infection:
•Suspected (as judged by PI) or confirmed COVID-19 within the last 2 weeks prior to Screening (Visit 1) or at Randomisation.
•Hospitalisation for COVID-19 within the last 12 weeks prior to Screening (Visit 1).
24. Any concomitant medications known to be a potent CYP3A4 inducers or inhibitors, eg, itraconazole, rifampicin, clarithromycin, or propylthiouracil
29. Previous enrolment and randomisation in the present study. (Participants who where screened and screen failed and not randomised in Part A can be screened for possible entry to Part B).
All exclusion criteria in Part A are applicable to Part B with the following exceptions:
Exclusion criteria 4; 19
Exclusion Criteria specific for Part B only [criteria numeration for Part B]
4. Life expectancy < 2 years due to other reasons than cardiovascular disease.
11. HF due to any of the following: known infiltrative cardiomyopathy (eg, amyloid, sarcoid, lymphoma, endomyocardial fibrosis), active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), or uncorrected primary valvular disease.
18. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening [Visit 1]).

Location

Research Site

Taipei 112, Taiwan, Province of China

Location

Research Site

Novosibirsk, Russian Federation, 630055

Location

Research Site

Kemerovo, Russian Federation, 650002

Location

Research Site

kaohsiung, Taiwan, Province of China, 807

Location

Research Site

St Petersburg, Russian Federation, 195067

Location

Research Site

Moscow, Russian Federation, 119991

Location

Research Site

Moscow, Russian Federation, 121552

Location

Research Site

North York, ON, Canada, M9N 1W4

Arms	Assigned Interventions
Experimental: Part A 2.5 mg AZD4831 2.5 mg	Drug: AZD4831 AZD4831
Experimental: Part A 5 mg AZD4831 5 mg	Drug: AZD4831 AZD4831
Placebo Comparator: Part A Placebo Placebo	Other: Placebo Placebo
Experimental: Part B Dose based on Part A AZD4831 Dose based on Part A	Drug: AZD4831 AZD4831
Placebo Comparator: Part B Placebo Placebo	Other: Placebo Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 142 study centres in 18 countries randomised participants.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Participant Flow: Overall Study

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
STARTED	235	240	236
COMPLETED	218	234	220
NOT COMPLETED	17	6	16
Death	10	3	10
Physician Decision	3	1	2
Withdrawal by Subject	4	2	4

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

All participants who have been randomised to study treatment and who have received at least one dose of investigational product were included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Baseline Measures

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo	Total
Number of Participants [units: Participants]	234	240	235	709
Age, Customized [units: Participants]
< 65 Years	34	42	30	106
65 - 75 Years	120	108	115	343
> 75 Years	80	90	90	260
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	16	14	21	51
Not Hispanic or Latino	218	226	214	658
Sex: Female, Male [units: Participants]
Female	107	119	96	322
Male	127	121	139	387
Race (NIH/OMB) [units: Participants]
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: Participants]
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
Age Continuous [units: Years] Mean ± Standard Deviation	72.5 ± 7.3	72.1 ± 7.1	72.5 ± 7.8	72.4 ± 7.4

Outcome Measures

1. Primary Outcome Measure: Kansas City Cardiomyopathy Questionnaire -Total Symptom Score [ Time Frame: Baseline - 16 weeks ]

Measure Type	Primary
Measure Name	Kansas City Cardiomyopathy Questionnaire -Total Symptom Score
Measure 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
Time Frame	Baseline - 16 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have been randomised to study treatment and who have received at least one dose of investigational product are included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

All participants who have been randomised to study treatment and who have received at least one dose of investigational product are included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	211	221	220
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score [units: Points] Least Squares Mean (95% Confidence Interval)	10.70 (8.58 to 12.82)	9.81 (7.73 to 11.90)	11.62 (9.54 to 13.71)

Statistical Analysis 1 for Kansas City Cardiomyopathy Questionnaire -Total Symptom Score

Groups^[1]	AZD4831 2.5 mg
Method^[3]	ANCOVA
P-Value^[4]	0.537
Mean Difference (Final Values)^[5]	-0.92
95% Confidence Interval	( -3.86 to 2.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Kansas City Cardiomyopathy Questionnaire -Total Symptom Score

Groups^[1]	AZD4831 5 mg
Method^[3]	ANCOVA
P-Value^[4]	0.221
Mean Difference (Final Values)^[5]	-1.81
95% Confidence Interval	( -4.71 to 1.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

2. Primary Outcome Measure: Six Minute Walk Distance [ Time Frame: Baseline - 16 weeks ]

Measure Type	Primary
Measure Name	Six Minute Walk Distance
Measure Description	Six Minute Walk Distance change from baseline at 16 weeks compared with placebo Part A
Time Frame	Baseline - 16 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have been randomised to study treatment and who have received at least one dose of investigational product were included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	210	223	223
Six Minute Walk Distance [units: Meters] Least Squares Mean (95% Confidence Interval)	15.3 (9.4 to 21.2)	18.2 (12.4 to 23.9)	12.9 (7.2 to 18.7)

Statistical Analysis 1 for Six Minute Walk Distance

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.559
Mean Difference (Final Values)^[5]	2.4
95% Confidence Interval	( -5.7 to 10.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Six Minute Walk Distance

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.195
Mean Difference (Final Values)^[5]	5.3
95% Confidence Interval	( -2.7 to 13.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

3. Secondary Outcome Measure: Kansas City Cardiomyopathy Questionnaire-Total Symptom Score [ Time Frame: Baseline - 24 and 48 weeks ]

Measure Type	Secondary
Measure Name	Kansas City Cardiomyopathy Questionnaire-Total Symptom Score
Measure 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.
Time Frame	Baseline - 24 and 48 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have been randomised to study treatment and who have received at least one dose of investigational product were included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Kansas City Cardiomyopathy Questionnaire-Total Symptom Score [units: Points] Least Squares Mean (95% Confidence Interval)
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score 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)
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score 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)

Statistical Analysis 1 for Kansas City Cardiomyopathy Questionnaire-Total Symptom Score

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.289
Mean Difference (Final Values)^[5]	-1.65
95% Confidence Interval	( -4.71 to 1.41 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Kansas City Cardiomyopathy Questionnaire-Total Symptom Score

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.571
Mean Difference (Final Values)^[5]	-0.87
95% Confidence Interval	( -3.86 to 2.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 3 for Kansas City Cardiomyopathy Questionnaire-Total Symptom Score

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.890
Mean Difference (Final Values)^[5]	-0.25
95% Confidence Interval	( -3.80 to 3.30 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for Kansas City Cardiomyopathy Questionnaire-Total Symptom Score

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.558
Mean Difference (Final Values)^[5]	-1.04
95% Confidence Interval	( -4.55 to 2.46 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

4. Secondary Outcome Measure: Six Minute Walk Distance [ Time Frame: Baseline - 24 and 48 weeks ]

Measure Type	Secondary
Measure Name	Six Minute Walk Distance
Measure Description	Six Minute Walk Distance change from baseline at 24 and 48 weeks compared with placebo Part A
Time Frame	Baseline - 24 and 48 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have been randomised to study treatment and who have received at least one dose of investigational product were included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Six Minute Walk Distance [units: Meters] Least Squares Mean (95% Confidence Interval)
Six Minute Walk Distance 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)
Six Minute Walk Distance 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)

Statistical Analysis 1 for Six Minute Walk Distance

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.619
Mean Difference (Final Values)^[5]	-2.2
95% Confidence Interval	( -11.1 to 6.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Six Minute Walk Distance

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.522
Mean Difference (Final Values)^[5]	2.8
95% Confidence Interval	( -5.8 to 11.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 3 for Six Minute Walk Distance

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.267
Mean Difference (Final Values)^[5]	5.7
95% Confidence Interval	( -4.4 to 15.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for Six Minute Walk Distance

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.657
Mean Difference (Final Values)^[5]	2.2
95% Confidence Interval	( -7.6 to 12.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

5. Secondary Outcome Measure: N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: Baseline - 16, 24 and 48 weeks ]

Measure Type	Secondary
Measure Name	N-terminal pro-brain natriuretic peptide (NT-proBNP)
Measure Description	NT-proBNP change from baseline at 16, 24, and 48 weeks compared with placebo Part A
Time Frame	Baseline - 16, 24 and 48 weeks
Safety Issue?

Population Description

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
N-terminal pro-brain natriuretic peptide (NT-proBNP) [units: ng/L] Geometric Least Squares Mean (95% Confidence Interval)
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)

Statistical Analysis 1 for N-terminal pro-brain natriuretic peptide (NT-proBNP)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.312
Mean Difference (Final Values)^[5]	0.95
95% Confidence Interval	( 0.86 to 1.05 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	NT-proBNP change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for N-terminal pro-brain natriuretic peptide (NT-proBNP)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.070
Mean Difference (Final Values)^[5]	0.91
95% Confidence Interval	( 0.83 to 1.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	NT-proBNP change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 3 for N-terminal pro-brain natriuretic peptide (NT-proBNP)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.911
Mean Difference (Final Values)^[5]	1.01
95% Confidence Interval	( 0.91 to 1.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	NT-proBNP change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for N-terminal pro-brain natriuretic peptide (NT-proBNP)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.837
Mean Difference (Final Values)^[5]	1.01
95% Confidence Interval	( 0.91 to 1.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	NT-proBNP change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 5 for N-terminal pro-brain natriuretic peptide (NT-proBNP)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.370
Mean Difference (Final Values)^[5]	0.95
95% Confidence Interval	( 0.84 to 1.07 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	NT-proBNP change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 6 for N-terminal pro-brain natriuretic peptide (NT-proBNP)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.205
Mean Difference (Final Values)^[5]	0.93
95% Confidence Interval	( 0.83 to 1.04 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	NT-proBNP change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

6. Secondary Outcome Measure: Left ventricular global longitudinal strain (LV-GLS) [ Time Frame: Baseline - 16 and 24 weeks ]

Measure Type	Secondary
Measure Name	Left ventricular global longitudinal strain (LV-GLS)
Measure Description	LV-GLS change from baseline at 16 and 24 weeks compared with placebo Part A
Time Frame	Baseline - 16 and 24 weeks
Safety Issue?

Population Description

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Left ventricular global longitudinal strain (LV-GLS) [units: Percentage (%)] Least Squares Mean (95% Confidence Interval)
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)

Statistical Analysis 1 for Left ventricular global longitudinal strain (LV-GLS)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.183
Mean Difference (Final Values)^[5]	0.5
95% Confidence Interval	( -0.2 to 1.2 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Left ventricular global longitudinal strain (LV-GLS)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.898
Mean Difference (Final Values)^[5]	0.0
95% Confidence Interval	( -0.8 to 0.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 3 for Left ventricular global longitudinal strain (LV-GLS)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.316
Mean Difference (Final Values)^[5]	0.4
95% Confidence Interval	( -0.4 to 1.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for Left ventricular global longitudinal strain (LV-GLS)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.934
Mean Difference (Final Values)^[5]	0.0
95% Confidence Interval	( -0.7 to 0.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

7. Secondary Outcome Measure: Left atrial volume index (LAVI) [ Time Frame: Baseline - 16 and 24 weeks ]

Measure Type	Secondary
Measure Name	Left atrial volume index (LAVI)
Measure Description	LAVI change from baseline at 16 and 24 weeks compared with placebo Part A
Time Frame	Baseline - 16 and 24 weeks
Safety Issue?

Population Description

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Left atrial volume index (LAVI) [units: mL/m2] Least Squares Mean (95% Confidence Interval)
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)

Statistical Analysis 1 for Left atrial volume index (LAVI)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.725
Mean Difference (Final Values)^[5]	0.360
95% Confidence Interval	( -1.647 to 2.366 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Left atrial volume index (LAVI)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.555
Mean Difference (Final Values)^[5]	-0.594
95% Confidence Interval	( -2.571 to 1.382 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 3 for Left atrial volume index (LAVI)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.586
Mean Difference (Final Values)^[5]	0.657
95% Confidence Interval	( -1.710 to 3.025 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for Left atrial volume index (LAVI)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.486
Mean Difference (Final Values)^[5]	-0.815
95% Confidence Interval	( -3.108 to 1.478 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

8. Secondary Outcome Measure: Left ventricular mass index (LVMI) [ Time Frame: Baseline - 16 and 24 weeks ]

Measure Type	Secondary
Measure Name	Left ventricular mass index (LVMI)
Measure Description	LVMI change from baseline at 16 and 24 weeks compared with placebo Part A
Time Frame	Baseline - 16 and 24 weeks
Safety Issue?

Population Description

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Left ventricular mass index (LVMI) [units: g/m2] Least Squares Mean (95% Confidence Interval)
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)

Statistical Analysis 1 for Left ventricular mass index (LVMI)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.968
Mean Difference (Final Values)^[5]	-0.1
95% Confidence Interval	( -4.1 to 3.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Left ventricular mass index (LVMI)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.251
Mean Difference (Final Values)^[5]	-2.3
95% Confidence Interval	( -6.3 to 1.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 3 for Left ventricular mass index (LVMI)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.872
Mean Difference (Final Values)^[5]	0.4
95% Confidence Interval	( -4.8 to 5.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Difference in adjusted mean change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for Left ventricular mass index (LVMI)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.682
Mean Difference (Final Values)^[5]	-1.1
95% Confidence Interval	( -6.2 to 4.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	No formal hypothesis testing and p-value is not adjusted for multiple comparisons.

9. Secondary Outcome Measure: Pharmacokinetics (AZD4831 plasma exposure) [ Time Frame: Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks, 48 weeks, 52 weeks ]

Measure Type	Secondary
Measure Name	Pharmacokinetics (AZD4831 plasma exposure)
Measure Description	Plasma concentrations of AZD4831 summarised by timepoint and dose level Part A
Time Frame	Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks, 48 weeks, 52 weeks
Safety Issue?

Population Description

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg
Number of Participants Analyzed [units:participants]	231	238
Pharmacokinetics (AZD4831 plasma exposure) [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%)

No statistical analysis provided for Pharmacokinetics (AZD4831 plasma exposure)

10. Secondary Outcome Measure: High sensitivity CRP (hsCRP) [ Time Frame: Baseline - 16, 24 and 48 weeks ]

Measure Type	Secondary
Measure Name	High sensitivity CRP (hsCRP)
Measure Description	hsCRP change from baseline at 16, 24, and 48 weeks compared with placebo Part A
Time Frame	Baseline - 16, 24 and 48 weeks
Safety Issue?

Population Description

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
High sensitivity CRP (hsCRP) [units: mg/dL] Geometric Least Squares Mean (95% Confidence Interval)
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)

Statistical Analysis 1 for High sensitivity CRP (hsCRP)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.760
Mean Difference (Final Values)^[5]	1.029
95% Confidence Interval	( 0.857 to 1.236 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for High sensitivity CRP (hsCRP)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.039
Mean Difference (Final Values)^[5]	1.209
95% Confidence Interval	( 1.010 to 1.448 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.

Statistical Analysis 3 for High sensitivity CRP (hsCRP)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.241
Mean Difference (Final Values)^[5]	1.111
95% Confidence Interval	( 0.931 to 1.326 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for High sensitivity CRP (hsCRP)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.049
Mean Difference (Final Values)^[5]	1.190
95% Confidence Interval	( 1.001 to 1.414 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 5 for High sensitivity CRP (hsCRP)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.158
Mean Difference (Final Values)^[5]	1.151
95% Confidence Interval	( 0.946 to 1.401 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 6 for High sensitivity CRP (hsCRP)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.131
Mean Difference (Final Values)^[5]	1.159
95% Confidence Interval	( 0.957 to 1.404 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

11. Secondary Outcome Measure: Interleukin 6 (IL-6) [ Time Frame: Baseline - 16, 24 and 48 weeks ]

Measure Type	Secondary
Measure Name	Interleukin 6 (IL-6)
Measure Description	IL-6 change from baseline at 16, 24, and 48 weeks compared with placebo Part A
Time Frame	Baseline - 16, 24 and 48 weeks
Safety Issue?

Population Description

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Interleukin 6 (IL-6) [units: ng/L] Geometric Least Squares Mean (95% Confidence Interval)
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)

Statistical Analysis 1 for Interleukin 6 (IL-6)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.874
Mean Difference (Final Values)^[5]	1.0111
95% Confidence Interval	( 0.8819 to 1.1592 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 2 for Interleukin 6 (IL-6)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.200
Mean Difference (Final Values)^[5]	0.9157
95% Confidence Interval	( 0.8002 to 1.0479 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 16 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 3 for Interleukin 6 (IL-6)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.135
Mean Difference (Final Values)^[5]	1.1063
95% Confidence Interval	( 0.9690 to 1.2631 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 4 for Interleukin 6 (IL-6)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.220
Mean Difference (Final Values)^[5]	1.0842
95% Confidence Interval	( 0.9527 to 1.2339 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 24 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 5 for Interleukin 6 (IL-6)

Groups^[1]	AZD4831 2.5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.467
Mean Difference (Final Values)^[5]	1.0496
95% Confidence Interval	( 0.9211 to 1.1960 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

Statistical Analysis 6 for Interleukin 6 (IL-6)

Groups^[1]	AZD4831 5 mg, Placebo
Method^[3]	ANCOVA
P-Value^[4]	0.636
Mean Difference (Final Values)^[5]	1.0312
95% Confidence Interval	( 0.9080 to 1.1711 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at 48 weeks
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Treatment group, neutrophil count stratification factor and the log-transformed baseline value are included in the model as explanatory variables.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Two-sided test.
[5]	Other relevant estimation information:
	Geometric mean ratio in change from baseline between AZD4831 and placebo.

12. Other Pre-specified Outcome Measure: Adverse Events [ Time Frame: Baseline - 52 weeks ]

Measure Type	Other Pre-specified
Measure Name	Adverse Events
Measure Description	Number of participants with Adverse Events Part A
Time Frame	Baseline - 52 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have received at least one dose of IP. Erroneously treated participants were accounted for in the treatment group of the treatment they actually received. A participants who received any dose of the active IP was classified as in the active IP treatment group. A participants who received both doses of active IP was classified as in the highest dose treatment group.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Adverse Events [units: Participants]	173	180	173

No statistical analysis provided for Adverse Events

13. Other Pre-specified Outcome Measure: Vital Signs [ Time Frame: Baseline - 52 weeks ]

Measure Type	Other Pre-specified
Measure Name	Vital Signs
Measure Description	Number of participants with treatment emergent vital sign abnormalities Part A
Time Frame	Baseline - 52 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have received at least one dose of IP. Erroneously treated participants were accounted for in the treatment group of the treatment they actually received. A participants who received any dose of the active IP was classified as in the active IP treatment group. A participants who received both doses of active IP was classified as in the highest dose treatment group.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Vital Signs [units: Participants]
Diastolic blood pressure >= 90 and increase from baseline >= 10 (mmHg)	62	60	68
Diastolic blood pressure < 60 and decrease from baseline >= 10 (mmHg)	32	42	33
Pulse rate >= 100 and increase from baseline >= 20 (beats/min)	15	17	11
Pulse rate < 50 and decrease from baseline >= 20 (beats/min)	2	6	8
Systolic blood pressure >= 140 and increase from baseline >= 20 (mmHg)	71	84	67
Systolic blood pressure < 90 and decrease from baseline >= 20 (mmHg)	5	3	3

No statistical analysis provided for Vital Signs

14. Other Pre-specified Outcome Measure: Clinical Laboratory [ Time Frame: Baseline - 52 weeks ]

Measure Type	Other Pre-specified
Measure Name	Clinical Laboratory
Measure Description	Number of participants with outliers for clinical laboratory measurements Part A
Time Frame	Baseline - 52 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have received at least one dose of IP. Erroneously treated participants were accounted for in the treatment group of the treatment they actually received. A participants who received any dose of the active IP was classified as in the active IP treatment group. A participants who received both doses of active IP was classified as in the highest dose treatment group.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Clinical Laboratory [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

No statistical analysis provided for Clinical Laboratory

15. Other Pre-specified Outcome Measure: Electrocardiogram (ECG) [ Time Frame: Baseline - 52 weeks ]

Measure Type	Other Pre-specified
Measure Name	Electrocardiogram (ECG)
Measure Description	Number of Participants With Abnormal ECG Last On-Study Value Part A
Time Frame	Baseline - 52 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who have received at least one dose of IP. Erroneously treated participants were accounted for in the treatment group of the treatment they actually received. A participants who received any dose of the active IP was classified as in the active IP treatment group. A participants who received both doses of active IP was classified as in the highest dose treatment group.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Measured Values

	AZD4831 2.5 mg	AZD4831 5 mg	Placebo
Number of Participants Analyzed [units:participants]	234	240	235
Electrocardiogram (ECG) [units: Participants]
Normal with Normal at baseline	43	52	49
Abnormal, not clinically significant with Normal at baseline	17	19	14
Abnormal, clinically significant last on-study value with Normal at baseline	2	0	1
Normal with Abnormal, not clinically significant at baseline	8	14	7
Abnormal, not clinically significant with Abnormal, not clinically significant at baseline	132	135	137
Abnormal, clinically significant with Abnormal, not clinically significant at baseline	5	2	4
Normal with Abnormal, clinically significant at baseline	0	0	1
Abnormal, not clinically significant with Abnormal, clinically significant at baseline	6	7	12
Abnormal, clinically significant with Abnormal, clinically significant at baseline	13	10	7

No statistical analysis provided for Electrocardiogram (ECG)

Serious Adverse Events

Time Frame	The on-study period (Baseline - 52 weeks). The on-study period for is calculated from the date of the first dose of IP and to the earliest date of withdrawal of consent or date of death. If withdrawal of consent or death did not occur, it is calculated from the date of the first dose of IP and to the last study visit.
Additional Description	No text entered.

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Serious Adverse Events

AZD4831 2.5 mg

AZD4831 5 mg

Placebo

Total, serious adverse events

# participants affected / at risk

60/234 (25.64%)

57/240 (23.75%)

56/235 (23.83%)

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

2/234 (0.85%)

5/240 (2.08%)

3/235 (1.28%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Metabolism and nutrition disorders

Hypophosphataemia¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Metabolism and nutrition disorders

Tumour lysis syndrome¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Musculoskeletal and connective tissue disorders

Arthritis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Osteoarthritis¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Rheumatoid arthritis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of colon¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Atrial flutter¹,^†

# participants affected / at risk

1/234 (0.43%)

1/240 (0.42%)

2/235 (0.85%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour pulmonary¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colorectal adenoma¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intraductal proliferative breast lesion¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Invasive ductal breast carcinoma¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lip squamous cell carcinoma¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma in situ¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma metastatic¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Plasma cell myeloma¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Atrial tachycardia¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Salivary gland neoplasm¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of lung¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Nervous system disorders

Cerebral haemorrhage¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Nervous system disorders

Cerebral infarction¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

0/234 (0.00%)

2/240 (0.83%)

0/235 (0.00%)

# events

Nervous system disorders

Dementia¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Nervous system disorders

Embolic stroke¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Nervous system disorders

Epilepsy¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Nervous system disorders

Ischaemic stroke¹,^†

# participants affected / at risk

3/234 (1.28%)

1/240 (0.42%)

1/235 (0.43%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

2/235 (0.85%)

# events

Nervous system disorders

Loss of consciousness¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Nervous system disorders

Optic neuritis¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

1/235 (0.43%)

# events

Nervous system disorders

Transient ischaemic attack¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Psychiatric disorders

Confusional state¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

1/235 (0.43%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

0/234 (0.00%)

2/240 (0.83%)

1/235 (0.43%)

# events

Renal and urinary disorders

Chronic kidney disease¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Renal and urinary disorders

Nephrotic syndrome¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

10/234 (4.27%)

13/240 (5.42%)

13/235 (5.53%)

# events

Renal and urinary disorders

Proteinuria¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Renal and urinary disorders

Renal failure¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

1/235 (0.43%)

# events

Renal and urinary disorders

Ureterolithiasis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchiectasis¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

1/234 (0.43%)

2/240 (0.83%)

0/235 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

2/235 (0.85%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Cardiac failure acute¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

2/235 (0.85%)

# events

Skin and subcutaneous tissue disorders

Erythema multiforme¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹,^†

# participants affected / at risk

0/234 (0.00%)

2/240 (0.83%)

0/235 (0.00%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Social circumstances

Alcohol use¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Vascular disorders

Aortic dissection¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Vascular disorders

Brachiocephalic arteriosclerosis¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

1/234 (0.43%)

1/240 (0.42%)

1/235 (0.43%)

# events

Vascular disorders

Iliac artery embolism¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Vascular disorders

Orthostatic hypotension¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Vascular disorders

Peripheral arterial occlusive disease¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Cardiac disorders

Cardiac failure chronic¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

3/235 (1.28%)

# events

Vascular disorders

Peripheral embolism¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Vascular disorders

Vascular insufficiency¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Vascular disorders

Vasculitis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Cardiac disorders

Cardiac failure congestive¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Cardiac tamponade¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Cardiac disorders

Cardiac valve disease¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Blood and lymphatic system disorders

Disseminated intravascular coagulation¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Cardiac disorders

Cardiomyopathy¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Coronary artery disease¹,^†

# participants affected / at risk

2/234 (0.85%)

0/240 (0.00%)

0/235 (0.00%)

# events

Cardiac disorders

Coronary artery stenosis¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Mitral valve incompetence¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Cardiac disorders

Mitral valve stenosis¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Pericarditis constrictive¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Cardiac disorders

Sinus node dysfunction¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

2/235 (0.85%)

# events

Cardiac disorders

Ventricular fibrillation¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Cardiac disorders

Ventricular tachycardia¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Ear and labyrinth disorders

Vestibular disorder¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

1/235 (0.43%)

# events

Blood and lymphatic system disorders

Immune thrombocytopenia¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Eye disorders

Blindness¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Eye disorders

Cataract¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Eye disorders

Scleritis¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Eye disorders

Vision blurred¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Gastrointestinal disorders

Abdominal strangulated hernia¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Gastrointestinal disorders

Duodenal ulcer perforation¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Gastrointestinal disorders

Enterocolitis¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Gastrointestinal disorders

Haematemesis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Gastrointestinal disorders

Hiatus hernia¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Blood and lymphatic system disorders

Iron deficiency anaemia¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Gastrointestinal disorders

Inguinal hernia¹,^†

# participants affected / at risk

2/234 (0.85%)

0/240 (0.00%)

0/235 (0.00%)

# events

Gastrointestinal disorders

Large intestine polyp¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Gastrointestinal disorders

Pancreatitis acute¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

1/235 (0.43%)

# events

Gastrointestinal disorders

Pneumoperitoneum¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Gastrointestinal disorders

Upper gastrointestinal haemorrhage¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

General disorders and administration site conditions

Death¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

General disorders and administration site conditions

Mucosal inflammation¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

General disorders and administration site conditions

Multiple organ dysfunction syndrome¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Blood and lymphatic system disorders

Normocytic anaemia¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

General disorders and administration site conditions

Sudden death¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Hepatobiliary disorders

Bile duct stone¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Hepatobiliary disorders

Cholecystitis acute¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Infections and infestations

Anal abscess¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Bacteraemia¹,^†

# participants affected / at risk

2/234 (0.85%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Covid-19¹,^†

# participants affected / at risk

3/234 (1.28%)

1/240 (0.42%)

0/235 (0.00%)

# events

Infections and infestations

Covid-19 pneumonia¹,^†

# participants affected / at risk

2/234 (0.85%)

2/240 (0.83%)

1/235 (0.43%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Cellulitis orbital¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Cardiac disorders

Acute left ventricular failure¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Infections and infestations

Citrobacter bacteraemia¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Infections and infestations

Erysipelas¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

1/235 (0.43%)

# events

Infections and infestations

Fournier's gangrene¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Gangrene¹,^†

# participants affected / at risk

2/234 (0.85%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Klebsiella urinary tract infection¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Osteomyelitis¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

2/235 (0.85%)

# events

Infections and infestations

Periodontitis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

2/234 (0.85%)

1/240 (0.42%)

2/235 (0.85%)

# events

Infections and infestations

Pneumonia bacterial¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

1/235 (0.43%)

# events

Infections and infestations

Pneumonia moraxella¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Pneumonia viral¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

3/235 (1.28%)

# events

Infections and infestations

Septic shock¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

1/235 (0.43%)

# events

Infections and infestations

Skin infection¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

2/234 (0.85%)

0/240 (0.00%)

0/235 (0.00%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

4/234 (1.71%)

0/240 (0.00%)

1/235 (0.43%)

# events

Infections and infestations

Urinary tract infection bacterial¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Infections and infestations

Wound infection bacterial¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Injury, poisoning and procedural complications

Chemical burn¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Concussion¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

1/234 (0.43%)

1/240 (0.42%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Injury, poisoning and procedural complications

Fracture¹,^†

# participants affected / at risk

2/234 (0.85%)

0/240 (0.00%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Radius fracture¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Road traffic accident¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Injury, poisoning and procedural complications

Scapula fracture¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Cardiac disorders

Angina unstable¹,^†

# participants affected / at risk

3/234 (1.28%)

3/240 (1.25%)

2/235 (0.85%)

# events

Injury, poisoning and procedural complications

Spinal compression fracture¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Subcutaneous haematoma¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Injury, poisoning and procedural complications

Thoracic vertebral fracture¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Injury, poisoning and procedural complications

Tibia fracture¹,^†

# participants affected / at risk

0/234 (0.00%)

0/240 (0.00%)

1/235 (0.43%)

# events

Injury, poisoning and procedural complications

Traumatic intracranial haemorrhage¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Vascular pseudoaneurysm¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Injury, poisoning and procedural complications

Wrist fracture¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Investigations

Blood sodium decreased¹,^†

# participants affected / at risk

0/234 (0.00%)

1/240 (0.42%)

0/235 (0.00%)

# events

Investigations

C-reactive protein increased¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

Investigations

Ejection fraction decreased¹,^†

# participants affected / at risk

1/234 (0.43%)

0/240 (0.00%)

0/235 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.0

Other Adverse Events

Time Frame	The on-study period (Baseline - 52 weeks). The on-study period for is calculated from the date of the first dose of IP and to the earliest date of withdrawal of consent or date of death. If withdrawal of consent or death did not occur, it is calculated from the date of the first dose of IP and to the last study visit.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0.05%

Reporting Groups

	Description
AZD4831 2.5 mg	Once-daily oral dosing of AZD4831 2.5 mg
AZD4831 5 mg	Once-daily oral dosing of AZD4831 5 mg
Placebo	Once-daily oral dosing of placebo

Other Adverse Events

AZD4831 2.5 mg

AZD4831 5 mg

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

49/234 (20.94%)

44/240 (18.33%)

45/235 (19.15%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

18/234 (7.69%)

10/240 (4.17%)

12/235 (5.11%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

11/234 (4.70%)

11/240 (4.58%)

14/235 (5.96%)

# events

Infections and infestations

Covid-19¹,^†

# participants affected / at risk

16/234 (6.84%)

18/240 (7.50%)

15/235 (6.38%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

9/234 (3.85%)

13/240 (5.42%)

15/235 (6.38%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
Redacted_CSP
Download
Redacted CSR synopsis
Download
D6580C00010_Redacted_SAP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Redacted_CSP

Redacted CSR synopsis