Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of AZD4831 in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40% (NCT NCT04986202)

NCT ID: NCT04986202

Last Updated: 2025-08-27

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 711 participants
• Primary outcome timeframe: Baseline - 16 weeks
• Results posted on: 2025-08-27

Participant Flow

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

Part B of the study was never started, results are only presented for Part A of the study. 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.

Participant milestones

Measure	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
Overall Study STARTED	235	240	236
Overall Study COMPLETED	218	234	220
Overall Study NOT COMPLETED	17	6	16

Reasons for withdrawal

Measure	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
Overall Study Death	10	3	10
Overall Study Physician Decision	3	1	2
Overall Study Withdrawal by Subject	4	2	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo	Total n=709 Participants Total of all reporting groups
Age, Continuous	72.5 Years STANDARD_DEVIATION 7.3 • n=93 Participants	72.1 Years STANDARD_DEVIATION 7.1 • n=4 Participants	72.5 Years STANDARD_DEVIATION 7.8 • n=27 Participants	72.4 Years STANDARD_DEVIATION 7.4 • n=483 Participants
Age, Customized < 65 Years	34 Participants n=93 Participants	42 Participants n=4 Participants	30 Participants n=27 Participants	106 Participants n=483 Participants
Age, Customized 65 - 75 Years	120 Participants n=93 Participants	108 Participants n=4 Participants	115 Participants n=27 Participants	343 Participants n=483 Participants
Age, Customized > 75 Years	80 Participants n=93 Participants	90 Participants n=4 Participants	90 Participants n=27 Participants	260 Participants n=483 Participants
Sex: Female, Male Female	107 Participants n=93 Participants	119 Participants n=4 Participants	96 Participants n=27 Participants	322 Participants n=483 Participants
Sex: Female, Male Male	127 Participants n=93 Participants	121 Participants n=4 Participants	139 Participants n=27 Participants	387 Participants n=483 Participants
Race/Ethnicity, Customized Hispanic or Latino	16 Participants n=93 Participants	14 Participants n=4 Participants	21 Participants n=27 Participants	51 Participants n=483 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	218 Participants n=93 Participants	226 Participants n=4 Participants	214 Participants n=27 Participants	658 Participants n=483 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race/Ethnicity, Customized Asian	35 Participants n=93 Participants	36 Participants n=4 Participants	36 Participants n=27 Participants	107 Participants n=483 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=93 Participants	10 Participants n=4 Participants	6 Participants n=27 Participants	21 Participants n=483 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race/Ethnicity, Customized White	193 Participants n=93 Participants	194 Participants n=4 Participants	192 Participants n=27 Participants	579 Participants n=483 Participants
Race/Ethnicity, Customized Other	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment Australia	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants
Region of Enrollment Belgium	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	9 Participants n=483 Participants
Region of Enrollment Brazil	13 Participants n=93 Participants	14 Participants n=4 Participants	15 Participants n=27 Participants	42 Participants n=483 Participants
Region of Enrollment Bulgaria	33 Participants n=93 Participants	32 Participants n=4 Participants	31 Participants n=27 Participants	96 Participants n=483 Participants
Region of Enrollment Canada	8 Participants n=93 Participants	8 Participants n=4 Participants	6 Participants n=27 Participants	22 Participants n=483 Participants
Region of Enrollment Czech Republic	23 Participants n=93 Participants	22 Participants n=4 Participants	22 Participants n=27 Participants	67 Participants n=483 Participants
Region of Enrollment Denmark	8 Participants n=93 Participants	9 Participants n=4 Participants	8 Participants n=27 Participants	25 Participants n=483 Participants
Region of Enrollment France	6 Participants n=93 Participants	7 Participants n=4 Participants	6 Participants n=27 Participants	19 Participants n=483 Participants
Region of Enrollment Hungary	18 Participants n=93 Participants	19 Participants n=4 Participants	19 Participants n=27 Participants	56 Participants n=483 Participants
Region of Enrollment Japan	25 Participants n=93 Participants	25 Participants n=4 Participants	25 Participants n=27 Participants	75 Participants n=483 Participants
Region of Enrollment Netherlands	4 Participants n=93 Participants	5 Participants n=4 Participants	5 Participants n=27 Participants	14 Participants n=483 Participants
Region of Enrollment Poland	22 Participants n=93 Participants	23 Participants n=4 Participants	24 Participants n=27 Participants	69 Participants n=483 Participants
Region of Enrollment Russian Federation	5 Participants n=93 Participants	5 Participants n=4 Participants	5 Participants n=27 Participants	15 Participants n=483 Participants
Region of Enrollment Slovakia	25 Participants n=93 Participants	26 Participants n=4 Participants	25 Participants n=27 Participants	76 Participants n=483 Participants
Region of Enrollment Sweden	12 Participants n=93 Participants	12 Participants n=4 Participants	13 Participants n=27 Participants	37 Participants n=483 Participants
Region of Enrollment Taiwan	10 Participants n=93 Participants	10 Participants n=4 Participants	10 Participants n=27 Participants	30 Participants n=483 Participants
Region of Enrollment Turkey	1 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	4 Participants n=483 Participants
Region of Enrollment United States of America	17 Participants n=93 Participants	17 Participants n=4 Participants	16 Participants n=27 Participants	50 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline - 16 weeks

Population: 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.

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

Outcome measures

Measure	AZD4831 2.5 mg n=211 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=221 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=220 Participants Once-daily oral dosing of placebo
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score	10.70 Points Interval 8.58 to 12.82	9.81 Points Interval 7.73 to 11.9	11.62 Points Interval 9.54 to 13.71

PRIMARY outcome

Timeframe: Baseline - 16 weeks

Population: 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.

Six Minute Walk Distance change from baseline at 16 weeks compared with placebo Part A

Outcome measures

Measure	AZD4831 2.5 mg n=210 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=223 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=223 Participants Once-daily oral dosing of placebo
Six Minute Walk Distance	15.3 Meters Interval 9.4 to 21.2	18.2 Meters Interval 12.4 to 23.9	12.9 Meters Interval 7.2 to 18.7

SECONDARY outcome

Timeframe: Baseline - 24 and 48 weeks

Population: 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.

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.

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
Kansas City Cardiomyopathy Questionnaire-Total Symptom Score Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 24 weeks	11.13 Points Interval 8.94 to 13.32	11.92 Points Interval 9.8 to 14.03	12.78 Points Interval 10.59 to 14.97
Kansas City Cardiomyopathy Questionnaire-Total Symptom Score Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 48 weeks	12.78 Points Interval 10.25 to 15.3	11.98 Points Interval 9.5 to 14.46	13.03 Points Interval 10.47 to 15.58

SECONDARY outcome

Timeframe: Baseline - 24 and 48 weeks

Population: 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.

Six Minute Walk Distance change from baseline at 24 and 48 weeks compared with placebo Part A

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
Six Minute Walk Distance Six Minute Walk Distance change from baseline at 24 weeks	13.5 Meters Interval 7.1 to 19.8	18.5 Meters Interval 12.4 to 24.6	15.7 Meters Interval 9.4 to 22.0
Six Minute Walk Distance Six Minute Walk Distance change from baseline at 48 weeks	19.2 Meters Interval 11.9 to 26.4	15.7 Meters Interval 8.6 to 22.7	13.5 Meters Interval 6.3 to 20.6

SECONDARY outcome

Timeframe: Baseline - 16, 24 and 48 weeks

Population: 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.

NT-proBNP change from baseline at 16, 24, and 48 weeks compared with placebo Part A

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) NT-proBNP change from baseline at 16 weeks	1.00 ng/L Interval 0.93 to 1.08	0.96 ng/L Interval 0.9 to 1.03	1.05 ng/L Interval 0.98 to 1.13
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) NT-proBNP change from baseline at 48 weeks	1.02 ng/L Interval 0.94 to 1.11	1.00 ng/L Interval 0.93 to 1.09	1.08 ng/L Interval 0.99 to 1.17
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) NT-proBNP change from baseline at 24 weeks	1.00 ng/L Interval 0.92 to 1.07	1.00 ng/L Interval 0.93 to 1.08	0.99 ng/L Interval 0.92 to 1.07

SECONDARY outcome

Timeframe: Baseline - 16 and 24 weeks

Population: 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.

LV-GLS change from baseline at 16 and 24 weeks compared with placebo Part A.

Left ventricular global longitudinal strain (LV-GLS) is an echocardiographic measure expressing longitudinal shortening as a percentage. A negative change from baseline indicates a better outcome.

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
Left Ventricular Global Longitudinal Strain (LV-GLS) LV-GLS change from baseline at 24 weeks	-0.6 Percentage (%) Interval -1.1 to 0.0	-0.9 Percentage (%) Interval -1.4 to -0.4	-1.0 Percentage (%) Interval -1.5 to -0.4
Left Ventricular Global Longitudinal Strain (LV-GLS) LV-GLS change from baseline at 16 weeks	0.1 Percentage (%) Interval -0.5 to 0.6	-0.5 Percentage (%) Interval -1.0 to 0.0	-0.4 Percentage (%) Interval -1.0 to 0.1

SECONDARY outcome

Timeframe: Baseline - 16 and 24 weeks

Population: 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.

LAVI change from baseline at 16 and 24 weeks compared with placebo Part A.

Left atrial volume index (LAVI) is an echocardiographic measure calculated by dividing LA volume by body surface area. A negative change from baseline indicates a better outcome.

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
Left Atrial Volume Index (LAVI) LAVI change from baseline at 24 weeks	1.096 mL/m2 Interval -0.626 to 2.818	-0.376 mL/m2 Interval -1.986 to 1.235	0.439 mL/m2 Interval -1.236 to 2.114
Left Atrial Volume Index (LAVI) LAVI change from baseline at 16 weeks	-0.940 mL/m2 Interval -2.373 to 0.493	-1.894 mL/m2 Interval -3.286 to -0.502	-1.300 mL/m2 Interval -2.743 to 0.144

SECONDARY outcome

Timeframe: Baseline - 16 and 24 weeks

Population: 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.

LVMI change from baseline at 16 and 24 weeks compared with placebo Part A.

Left ventricular mass index (LVMI) is an echocardiographic measure calculated by dividing LVM by body surface area. A negative change from baseline indicates a better outcome.

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
Left Ventricular Mass Index (LVMI) LVMI change from baseline at 16 weeks	1.3 g/m2 Interval -1.6 to 4.2	-0.9 g/m2 Interval -3.8 to 1.9	1.4 g/m2 Interval -1.5 to 4.2
Left Ventricular Mass Index (LVMI) LVMI change from baseline at 24 weeks	9.8 g/m2 Interval 6.0 to 13.5	8.3 g/m2 Interval 4.6 to 11.9	9.4 g/m2 Interval 5.6 to 13.1

SECONDARY outcome

Timeframe: Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks, 48 weeks, 52 weeks

Population: 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.

Plasma concentrations of AZD4831 summarised by timepoint and dose level Part A

Outcome measures

Measure	AZD4831 2.5 mg n=231 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=238 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo Once-daily oral dosing of placebo
Pharmacokinetics (AZD4831 Plasma Exposure) Baseline (pre-dose)	1.02 nmol/L Geometric Coefficient of Variation 19.57	1.01 nmol/L Geometric Coefficient of Variation 9.38	—
Pharmacokinetics (AZD4831 Plasma Exposure) 4 weeks (pre-dose)	14.45 nmol/L Geometric Coefficient of Variation 99.26	26.44 nmol/L Geometric Coefficient of Variation 141.88	—
Pharmacokinetics (AZD4831 Plasma Exposure) 12 weeks (pre-dose)	13.51 nmol/L Geometric Coefficient of Variation 130.33	25.45 nmol/L Geometric Coefficient of Variation 161.09	—
Pharmacokinetics (AZD4831 Plasma Exposure) 16 weeks (pre-dose)	13.59 nmol/L Geometric Coefficient of Variation 126.71	25.31 nmol/L Geometric Coefficient of Variation 159.79	—
Pharmacokinetics (AZD4831 Plasma Exposure) 24 weeks (pre-dose)	12.87 nmol/L Geometric Coefficient of Variation 146.45	23.08 nmol/L Geometric Coefficient of Variation 199.18	—
Pharmacokinetics (AZD4831 Plasma Exposure) 48 weeks (pre-dose)	10.36 nmol/L Geometric Coefficient of Variation 188.55	21.18 nmol/L Geometric Coefficient of Variation 229.28	—
Pharmacokinetics (AZD4831 Plasma Exposure) 52 weeks (pre-dose)	1.14 nmol/L Geometric Coefficient of Variation 49.22	1.27 nmol/L Geometric Coefficient of Variation 74.56	—

SECONDARY outcome

Timeframe: Baseline - 16, 24 and 48 weeks

Population: 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.

hsCRP change from baseline at 16, 24, and 48 weeks compared with placebo Part A

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
High Sensitivity CRP (hsCRP) hsCRP change from baseline at 24 weeks	1.029 mg/dL Interval 0.907 to 1.168	1.101 mg/dL Interval 0.976 to 1.243	0.926 mg/dL Interval 0.816 to 1.051
High Sensitivity CRP (hsCRP) hsCRP change from baseline at 16 weeks	0.940 mg/dL Interval 0.824 to 1.073	1.105 mg/dL Interval 0.971 to 1.257	0.914 mg/dL Interval 0.802 to 1.041
High Sensitivity CRP (hsCRP) hsCRP change from baseline at 48 weeks	1.120 mg/dL Interval 0.973 to 1.288	1.127 mg/dL Interval 0.985 to 1.29	0.972 mg/dL Interval 0.845 to 1.119

SECONDARY outcome

Timeframe: Baseline - 16, 24 and 48 weeks

Population: 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.

IL-6 change from baseline at 16, 24, and 48 weeks compared with placebo Part A

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
Interleukin 6 (IL-6) IL-6 change from baseline at 16 weeks	1.1326 ng/L Interval 1.0261 to 1.2502	1.0258 ng/L Interval 0.9316 to 1.1295	1.1202 ng/L Interval 1.017 to 1.2339
Interleukin 6 (IL-6) IL-6 change from baseline at 24 weeks	1.0918 ng/L Interval 0.9934 to 1.2	1.0700 ng/L Interval 0.9777 to 1.1711	0.9869 ng/L Interval 0.8975 to 1.0852
Interleukin 6 (IL-6) IL-6 change from baseline at 48 weeks	1.3328 ng/L Interval 1.2134 to 1.4639	1.3094 ng/L Interval 1.1972 to 1.4321	1.2698 ng/L Interval 1.1574 to 1.3931

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline - 52 weeks

Population: All participants who received at least one dose of IP. Participants treated in error were accounted for in the treatment group of the treatment actually received. A participant who received any dose of the active IP was classified as in the active IP treatment group. A participant who received both doses of active IP was classified as in the highest dose treatment group.

Number of participants with Adverse Events Part A

Outcome measures

Measure	AZD4831 2.5 mg n=234 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 Participants Once-daily oral dosing of placebo
Adverse Events	173 Participants	180 Participants	173 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline - 52 weeks

Population: All participants who received at least one dose of IP. Participants treated in error were accounted for in the treatment group of the treatment actually received. A participant who received any dose of the active IP was classified as in the active IP treatment group. A participant who received both doses of active IP was classified as in the highest dose treatment group. Number analyzed is the number of participants per treatment group with a baseline value and at least one post-baseline value.

Number of participants with treatment emergent vital sign abnormalities Part A

Outcome measures

Measure	AZD4831 2.5 mg n=233 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=234 Participants Once-daily oral dosing of placebo
Vital Signs Systolic blood pressure < 90 and decrease from baseline >= 20 (mmHg)	5 Participants	3 Participants	3 Participants
Vital Signs Pulse rate < 50 and decrease from baseline >= 20 (beats/min)	2 Participants	6 Participants	8 Participants
Vital Signs Systolic blood pressure >= 140 and increase from baseline >= 20 (mmHg)	71 Participants	84 Participants	67 Participants
Vital Signs Diastolic blood pressure >= 90 and increase from baseline >= 10 (mmHg)	62 Participants	60 Participants	68 Participants
Vital Signs Diastolic blood pressure < 60 and decrease from baseline >= 10 (mmHg)	32 Participants	42 Participants	33 Participants
Vital Signs Pulse rate >= 100 and increase from baseline >= 20 (beats/min)	15 Participants	17 Participants	11 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline - 52 weeks

Population: All participants who received at least one dose of IP. Participants treated in error were accounted for in the treatment group of the treatment actually received. A participant who received any dose of the active IP was classified as in the active IP treatment group. A participant who received both doses of active IP was classified as in the highest dose treatment group. Number analyzed is the number of participants per treatment group with a baseline value and at least one post-baseline value.

Number of participants with outliers for clinical laboratory (chemistry) measurements Part A

Outcome measures

Measure	AZD4831 2.5 mg n=227 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=238 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=232 Participants Once-daily oral dosing of placebo
Clinical Laboratory (Haematology) Eosinophils >= 0.7 (10^9/L)	4 Participants	4 Participants	8 Participants
Clinical Laboratory (Haematology) Eosinophils >= 1.5 (10^9/L)	0 Participants	0 Participants	0 Participants
Clinical Laboratory (Haematology) Hemoglobin < 80 (g/L)	1 Participants	1 Participants	0 Participants
Clinical Laboratory (Haematology) Neutrophil count < 1.5 (10^9/L)	2 Participants	7 Participants	3 Participants
Clinical Laboratory (Haematology) Leukocytes < 3.0 (10^9/L)	3 Participants	5 Participants	6 Participants
Clinical Laboratory (Haematology) Leukocytes < 2.0 (10^9/L)	0 Participants	1 Participants	0 Participants
Clinical Laboratory (Haematology) Hemoglobin < 100 (g/L)	9 Participants	11 Participants	6 Participants
Clinical Laboratory (Haematology) Neutrophil count < 1.0 (10^9/L)	0 Participants	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline - 52 weeks

Population: All participants who received at least one dose of IP. Participants treated in error were accounted for in the treatment group of the treatment actually received. A participant who received any dose of the active IP was classified as in the active IP treatment group. A participant who received both doses of active IP was classified as in the highest dose treatment group. Number analyzed is the number of participants per treatment group with a baseline value and at least one post-baseline value.

Number of participants with outliers for clinical laboratory (chemistry) measurements Part A

Outcome measures

Measure	AZD4831 2.5 mg n=227 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=239 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=232 Participants Once-daily oral dosing of placebo
Clinical Laboratory (Chemistry) Creatinine >= 2x baseline creatinine	3 Participants	0 Participants	2 Participants
Clinical Laboratory (Chemistry) TSH >6 (mIU/L)	19 Participants	25 Participants	18 Participants
Clinical Laboratory (Chemistry) TSH >=10 (mIU/L)	12 Participants	6 Participants	3 Participants
Clinical Laboratory (Chemistry) TSH > 6 and free T4 < LLN (mIU/L)	2 Participants	1 Participants	0 Participants
Clinical Laboratory (Chemistry) TSH >= 10 and free T4 < LLN (mIU/L)	2 Participants	0 Participants	0 Participants
Clinical Laboratory (Chemistry) ALP > 1.5x ULN	9 Participants	8 Participants	13 Participants
Clinical Laboratory (Chemistry) ALP > 3x ULN	0 Participants	0 Participants	1 Participants
Clinical Laboratory (Chemistry) ALT > 3x ULN	5 Participants	2 Participants	3 Participants
Clinical Laboratory (Chemistry) ALT > 5x ULN	2 Participants	0 Participants	1 Participants
Clinical Laboratory (Chemistry) ALT > 10x ULN	0 Participants	0 Participants	0 Participants
Clinical Laboratory (Chemistry) AST > 3x ULN	3 Participants	3 Participants	4 Participants
Clinical Laboratory (Chemistry) AST > 5x ULN	1 Participants	0 Participants	0 Participants
Clinical Laboratory (Chemistry) AST > 10x ULN	0 Participants	0 Participants	0 Participants
Clinical Laboratory (Chemistry) Creatinine >= 1.5x baseline creatinine	15 Participants	10 Participants	14 Participants
Clinical Laboratory (Chemistry) TB > 1.5x ULN	6 Participants	1 Participants	12 Participants
Clinical Laboratory (Chemistry) TB > 2x ULN	1 Participants	1 Participants	2 Participants
Clinical Laboratory (Chemistry) AST or ALT > 3x ULN	6 Participants	3 Participants	4 Participants
Clinical Laboratory (Chemistry) AST or ALT > 3x ULN and TB > 2x ULN	0 Participants	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline - 52 weeks

Population: All participants who received at least one dose of IP. Participants treated in error were accounted for in the treatment group of the treatment actually received. A participant who received any dose of the active IP was classified as in the active IP treatment group. A participant who received both doses of active IP was classified as in the highest dose treatment group. Number analyzed is the number of participants per treatment group with a baseline value and at least one post-baseline value.

Number of Participants With Abnormal ECG Last On-Study Value Part A

Outcome measures

Measure	AZD4831 2.5 mg n=226 Participants Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=239 Participants Once-daily oral dosing of AZD4831 5 mg	Placebo n=232 Participants Once-daily oral dosing of placebo
Electrocardiogram (ECG) Normal with Abnormal, not clinically significant at baseline	8 Participants	14 Participants	7 Participants
Electrocardiogram (ECG) Abnormal, not clinically significant with Abnormal, not clinically significant at baseline	132 Participants	135 Participants	137 Participants
Electrocardiogram (ECG) Abnormal, clinically significant with Abnormal, not clinically significant at baseline	5 Participants	2 Participants	4 Participants
Electrocardiogram (ECG) Normal with Normal at baseline	43 Participants	52 Participants	49 Participants
Electrocardiogram (ECG) Abnormal, not clinically significant with Normal at baseline	17 Participants	19 Participants	14 Participants
Electrocardiogram (ECG) Abnormal, clinically significant last on-study value with Normal at baseline	2 Participants	0 Participants	1 Participants
Electrocardiogram (ECG) Normal with Abnormal, clinically significant at baseline	0 Participants	0 Participants	1 Participants
Electrocardiogram (ECG) Abnormal, not clinically significant with Abnormal, clinically significant at baseline	6 Participants	7 Participants	12 Participants
Electrocardiogram (ECG) Abnormal, clinically significant with Abnormal, clinically significant at baseline	13 Participants	10 Participants	7 Participants

Adverse Events

AZD4831 2.5 mg

Serious events: 60 serious events

Other events: 49 other events

Deaths: 10 deaths

AZD4831 5 mg

Serious events: 57 serious events

Other events: 44 other events

Deaths: 3 deaths

Placebo

Serious events: 56 serious events

Other events: 45 other events

Deaths: 10 deaths

Serious adverse events

Measure	AZD4831 2.5 mg n=234 participants at risk Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 participants at risk Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 participants at risk Once-daily oral dosing of placebo
Infections and infestations Bronchitis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Covid-19	1.3% 3/234 • Number of events 3 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Infections and infestations Covid-19 pneumonia	0.85% 2/234 • Number of events 2 • 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.	0.83% 2/240 • Number of events 2 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Cellulitis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
General disorders Chest pain	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
General disorders Death	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
General disorders Mucosal inflammation	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
General disorders Multiple organ dysfunction syndrome	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Blood and lymphatic system disorders Normocytic anaemia	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
General disorders Sudden death	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Hepatobiliary disorders Bile duct stone	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 2 • 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.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Infections and infestations Anal abscess	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Bacteraemia	0.85% 2/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Atrial fibrillation	0.85% 2/234 • Number of events 2 • 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.	2.1% 5/240 • Number of events 6 • 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.	1.3% 3/235 • Number of events 3 • 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.
Metabolism and nutrition disorders Dehydration	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Metabolism and nutrition disorders Tumour lysis syndrome	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Arthritis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Cardiac disorders Atrial flutter	0.43% 1/234 • Number of events 1 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.85% 2/235 • Number of events 2 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour pulmonary	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal adenoma	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip squamous cell carcinoma	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Cardiac disorders Atrial tachycardia	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland neoplasm	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Nervous system disorders Cerebral haemorrhage	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Nervous system disorders Cerebral infarction	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Nervous system disorders Cerebrovascular accident	0.00% 0/234 • 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.	0.83% 2/240 • Number of events 2 • 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.	0.00% 0/235 • 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.
Nervous system disorders Dementia	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Nervous system disorders Dizziness	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Nervous system disorders Embolic stroke	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Nervous system disorders Epilepsy	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Nervous system disorders Ischaemic stroke	1.3% 3/234 • Number of events 3 • 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.	0.42% 1/240 • Number of events 2 • 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.	0.43% 1/235 • Number of events 1 • 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.
Cardiac disorders Cardiac arrest	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.85% 2/235 • Number of events 2 • 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.
Nervous system disorders Loss of consciousness	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Nervous system disorders Optic neuritis	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Nervous system disorders Paraesthesia	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Nervous system disorders Syncope	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Nervous system disorders Transient ischaemic attack	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Psychiatric disorders Confusional state	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Psychiatric disorders Depression	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Renal and urinary disorders Acute kidney injury	0.00% 0/234 • 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.	0.83% 2/240 • Number of events 2 • 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.	0.43% 1/235 • Number of events 1 • 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.
Renal and urinary disorders Chronic kidney disease	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Renal and urinary disorders Nephrotic syndrome	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Cardiac failure	4.3% 10/234 • Number of events 11 • 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.	5.4% 13/240 • Number of events 16 • 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.	5.5% 13/235 • Number of events 15 • 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.
Renal and urinary disorders Proteinuria	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Renal and urinary disorders Renal failure	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.43% 1/235 • Number of events 1 • 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.
Renal and urinary disorders Ureterolithiasis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.43% 1/234 • Number of events 3 • 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.	0.83% 2/240 • Number of events 3 • 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.	0.00% 0/235 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.85% 2/235 • Number of events 2 • 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.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Cardiac disorders Cardiac failure acute	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.85% 2/235 • Number of events 2 • 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.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/234 • 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.	0.83% 2/240 • Number of events 2 • 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.	0.00% 0/235 • 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.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Social circumstances Alcohol use	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Vascular disorders Aortic dissection	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Vascular disorders Brachiocephalic arteriosclerosis	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Vascular disorders Hypotension	0.43% 1/234 • Number of events 1 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.43% 1/235 • Number of events 1 • 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.
Vascular disorders Iliac artery embolism	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Vascular disorders Orthostatic hypotension	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Cardiac disorders Cardiac failure chronic	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	1.3% 3/235 • Number of events 4 • 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.
Vascular disorders Peripheral embolism	0.43% 1/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Vascular disorders Vascular insufficiency	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Vascular disorders Vasculitis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Cardiac failure congestive	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 2 • 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.	0.00% 0/235 • 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.
Cardiac disorders Cardiac tamponade	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Cardiac valve disease	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Cardiomyopathy	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Cardiac disorders Coronary artery disease	0.85% 2/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Coronary artery stenosis	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Cardiac disorders Mitral valve incompetence	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Cardiac disorders Mitral valve stenosis	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Cardiac disorders Pericarditis constrictive	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Cardiac disorders Sinus node dysfunction	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.85% 2/235 • Number of events 2 • 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.
Cardiac disorders Ventricular fibrillation	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Cardiac disorders Ventricular tachycardia	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Ear and labyrinth disorders Vestibular disorder	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Blood and lymphatic system disorders Immune thrombocytopenia	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Eye disorders Blindness	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Eye disorders Cataract	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Eye disorders Scleritis	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Eye disorders Vision blurred	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Gastrointestinal disorders Abdominal strangulated hernia	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Gastrointestinal disorders Enterocolitis	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Gastrointestinal disorders Haematemesis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Gastrointestinal disorders Hiatus hernia	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Gastrointestinal disorders Ileus	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Gastrointestinal disorders Inguinal hernia	0.85% 2/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Gastrointestinal disorders Large intestine polyp	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.43% 1/235 • Number of events 1 • 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.
Gastrointestinal disorders Pneumoperitoneum	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Cellulitis orbital	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Cardiac disorders Acute left ventricular failure	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Citrobacter bacteraemia	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Diverticulitis	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Infections and infestations Erysipelas	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Fournier's gangrene	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Gangrene	0.85% 2/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Influenza	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Klebsiella urinary tract infection	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Osteomyelitis	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.85% 2/235 • Number of events 2 • 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.
Infections and infestations Periodontitis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Acute myocardial infarction	0.43% 1/234 • Number of events 3 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Pneumonia	0.85% 2/234 • Number of events 2 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.85% 2/235 • Number of events 2 • 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.
Infections and infestations Pneumonia bacterial	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Pneumonia moraxella	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Pneumonia viral	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Infections and infestations Pyelonephritis	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Infections and infestations Sepsis	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	1.3% 3/235 • Number of events 3 • 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.
Infections and infestations Septic shock	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Skin infection	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Upper respiratory tract infection	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Urinary tract infection	0.85% 2/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Cardiac disorders Angina pectoris	1.7% 4/234 • Number of events 4 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Infections and infestations Urinary tract infection bacterial	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Infections and infestations Wound infection bacterial	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Injury, poisoning and procedural complications Chemical burn	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Concussion	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Fall	0.43% 1/234 • Number of events 4 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Injury, poisoning and procedural complications Fracture	0.85% 2/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Radius fracture	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Cardiac disorders Angina unstable	1.3% 3/234 • Number of events 4 • 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.	1.2% 3/240 • Number of events 3 • 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.	0.85% 2/235 • Number of events 2 • 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.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/234 • 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.	0.00% 0/240 • 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.	0.43% 1/235 • Number of events 1 • 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.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Injury, poisoning and procedural complications Wrist fracture	0.43% 1/234 • Number of events 2 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Investigations Blood sodium decreased	0.00% 0/234 • 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.	0.42% 1/240 • Number of events 1 • 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.	0.00% 0/235 • 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.
Investigations C-reactive protein increased	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.
Investigations Ejection fraction decreased	0.43% 1/234 • Number of events 1 • 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.	0.00% 0/240 • 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.	0.00% 0/235 • 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.

Other adverse events

Measure	AZD4831 2.5 mg n=234 participants at risk Once-daily oral dosing of AZD4831 2.5 mg	AZD4831 5 mg n=240 participants at risk Once-daily oral dosing of AZD4831 5 mg	Placebo n=235 participants at risk Once-daily oral dosing of placebo
Nervous system disorders Dizziness	7.7% 18/234 • Number of events 21 • 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.	4.2% 10/240 • Number of events 12 • 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.	5.1% 12/235 • Number of events 15 • 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.
Cardiac disorders Cardiac failure	4.7% 11/234 • Number of events 14 • 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.	4.6% 11/240 • Number of events 13 • 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.	6.0% 14/235 • Number of events 14 • 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.
Infections and infestations Covid-19	6.8% 16/234 • Number of events 16 • 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.	7.5% 18/240 • Number of events 18 • 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.	6.4% 15/235 • Number of events 15 • 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.
Infections and infestations Nasopharyngitis	3.8% 9/234 • Number of events 12 • 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.	5.4% 13/240 • Number of events 15 • 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.	6.4% 15/235 • Number of events 21 • 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 Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place