Trial Outcomes & Findings for A Study of Cotadutide in Participants Who Have Chronic Kidney Disease With Type 2 Diabetes Mellitus (NCT NCT04515849)

NCT ID: NCT04515849

Last Updated: 2025-01-17

Results Overview

Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks. Efficacy endpoints for cotadutide vs. semaglutide are exploratory and are therefore excluded.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 248 participants
• Primary outcome timeframe: Baseline to the end of 14 weeks of dosing
• Results posted on: 2025-01-17

Participant Flow

This study was conducted at 79 participating sites in Canada, Australia, New Zealand, Japan, Germany, Poland, Spain and United Kingdom. First subject enrolled 31st August 2020. Last subject last visit: 8th March 2022.

This is a parallel treatment, double-blind study with 5 arms: Cotadutide 100 mcg,300 mcg&600 mcg,placebo and an open-label semaglutide arm.Outcomes for the cotadutide arms vs. semaglutide were exploratory.Therefore semaglutide arm was excluded from Outcomes.248 patients were enrolled.The study had a 14-day run-in period during which participants followed by a 26-week treatment period and 28-day follow-up period.

Participant milestones

Measure	Cotadutide 100 ug Participants randomised to cotadutide 100 µg daily	Cotadutide 300 ug Participants randomised to Cotadutide 300 ug daily	Cotadutide 600 ug Participants randomised to Cotadutide 600 ug daily	Placebo ug Participants randomised to placebo daily	Semaglutide 1 mg Participants randomized to semaglutide 1 mg weekly
Overall Study STARTED	52	49	51	51	45
Overall Study COMPLETED	49	45	50	48	43
Overall Study NOT COMPLETED	3	4	1	3	2

Reasons for withdrawal

Measure	Cotadutide 100 ug Participants randomised to cotadutide 100 µg daily	Cotadutide 300 ug Participants randomised to Cotadutide 300 ug daily	Cotadutide 600 ug Participants randomised to Cotadutide 600 ug daily	Placebo ug Participants randomised to placebo daily	Semaglutide 1 mg Participants randomized to semaglutide 1 mg weekly
Overall Study Adverse Event	0	0	0	1	2
Overall Study Death	2	0	0	0	0
Overall Study Other:family emergency	0	0	0	1	0
Overall Study Other:randomised by error	0	1	0	0	0
Overall Study Other:subject hasa to fly to greece for a family emergency and will not be back till 4-5 months	0	0	0	1	0
Overall Study Physician Decision	0	1	0	0	0
Overall Study Withdrawal by Subject	1	2	1	0	0

Baseline Characteristics

A Study of Cotadutide in Participants Who Have Chronic Kidney Disease With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Cotadutide 100 ug n=52 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 ug n=49 Participants Participants randomised to Cotadutide 300 ug daily	Cotadutide 600 ug n=51 Participants Participants randomised to Cotadutide 600 ug daily	Placebo ug n=51 Participants Participants randomised to placebo daily	Semaglutide 1 mg n=45 Participants Participants randomized to semaglutide 1 mg weekly	Total n=248 Participants Total of all reporting groups
Age, Continuous	67.2 Years STANDARD_DEVIATION 7.3 • n=5 Participants	65.7 Years STANDARD_DEVIATION 8.8 • n=7 Participants	66.1 Years STANDARD_DEVIATION 7.4 • n=5 Participants	69.5 Years STANDARD_DEVIATION 7.3 • n=4 Participants	67.0 Years STANDARD_DEVIATION 7.8 • n=21 Participants	67.1 Years STANDARD_DEVIATION 7.8 • n=8 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants	13 Participants n=4 Participants	12 Participants n=21 Participants	47 Participants n=8 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	46 Participants n=7 Participants	41 Participants n=5 Participants	38 Participants n=4 Participants	33 Participants n=21 Participants	201 Participants n=8 Participants
Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race/Ethnicity, Customized ASIAN	10 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants	10 Participants n=4 Participants	2 Participants n=21 Participants	45 Participants n=8 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	5 Participants n=8 Participants
Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=8 Participants
Race/Ethnicity, Customized OTHER	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=8 Participants
Race/Ethnicity, Customized WHITE	38 Participants n=5 Participants	36 Participants n=7 Participants	36 Participants n=5 Participants	39 Participants n=4 Participants	41 Participants n=21 Participants	190 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline to the end of 14 weeks of dosing

Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks. Efficacy endpoints for cotadutide vs. semaglutide are exploratory and are therefore excluded.

Outcome measures

Measure	Cotadutide 100 ug n=49 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=43 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=37 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=43 Participants Participants randomised to placebo daily
The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks	-10.96 Percentage change Interval -29.6 to 12.61	-40.47 Percentage change Interval -53.0 to -24.6	-44.60 Percentage change Interval -56.21 to -29.91	4.60 Percentage change Interval -18.02 to 33.46

SECONDARY outcome

Timeframe: Baseline to end of 26 weeks of dosing

Percentage change in UACR of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks. Efficacy endpoints for cotadutide vs. semaglutide are exploratory and are therefore excluded.

Outcome measures

Measure	Cotadutide 100 ug n=49 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=46 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=48 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=49 Participants Participants randomised to placebo daily
Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks	-17.85 Percentage change Interval -45.47 to 23.78	-38.68 Percentage change Interval -59.61 to -6.88	-57.87 Percentage change Interval -73.33 to -33.45	11.79 Percentage change Interval -27.85 to 73.22

SECONDARY outcome

Timeframe: Baseline to end of 14 weeks of dosing

Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing.

Outcome measures

Measure	Cotadutide 100 ug n=37 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=32 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=27 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=35 Participants Participants randomised to placebo daily
Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing	-2.84 Percentage change Standard Error 0.65	-4.15 Percentage change Standard Error 0.68	-5.40 Percentage change Standard Error 0.73	-1.61 Percentage change Standard Error 0.66

SECONDARY outcome

Timeframe: Baseline to end of 26 weeks of dosing

Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing

Outcome measures

Measure	Cotadutide 100 ug n=37 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=33 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=27 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=35 Participants Participants randomised to placebo daily
Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing	-2.60 Percentage change Standard Error 0.89	-5.45 Percentage change Standard Error 0.92	-7.35 Percentage change Standard Error 0.99	-2.23 Percentage change Standard Error 0.90

SECONDARY outcome

Timeframe: Baseline to end of 14 weeks of dosing

Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing

Outcome measures

Measure	Cotadutide 100 ug n=49 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=45 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=48 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=39 Participants Participants randomised to placebo daily
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing	-0.76 Percent change Standard Error 0.12	-0.82 Percent change Standard Error 0.12	-0.65 Percent change Standard Error 0.12	-0.08 Percent change Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline to end of 26 weeks of dosing

Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing

Outcome measures

Measure	Cotadutide 100 ug n=49 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=46 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=48 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=39 Participants Participants randomised to placebo daily
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing	-0.92 Percent change Standard Error 0.11	-0.92 Percent change Standard Error 0.11	-0.89 Percent change Standard Error 0.11	-0.25 Percent change Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline to end of 14 weeks of dosing

Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks

Outcome measures

Measure	Cotadutide 100 ug n=42 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=45 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=48 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=49 Participants Participants randomised to placebo daily
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing	-1.35 mmol/L Standard Error 0.37	-1.57 mmol/L Standard Error 0.35	-1.69 mmol/L Standard Error 0.40	-0.54 mmol/L Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline to end of 26 weeks of dosing

Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks

Outcome measures

Measure	Cotadutide 100 ug n=45 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=43 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=39 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=45 Participants Participants randomised to placebo daily
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing	-1.78 mmol/L Standard Error 0.36	-1.76 mmol/L Standard Error 0.37	-1.57 mmol/L Standard Error 0.39	-0.72 mmol/L Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline to end of 14 weeks of dosing

Absolute change in 10-day average glucose of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing

Outcome measures

Measure	Cotadutide 100 ug n=30 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=25 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=26 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=30 Participants Participants randomised to placebo daily
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing	-1.556 mmol/L Standard Error 0.320	-1.478 mmol/L Standard Error 0.337	-1.269 mmol/L Standard Error 0.334	-0.440 mmol/L Standard Error 0.311

SECONDARY outcome

Timeframe: Baseline to end of 26 weeks of dosing

Absolute change in 10-day average glucose of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing

Outcome measures

Measure	Cotadutide 100 ug n=25 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=18 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=22 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=30 Participants Participants randomised to placebo daily
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing	-1.735 mmol/L Standard Error 0.307	-1.446 mmol/L Standard Error 0.334	-1.118 mmol/L Standard Error 0.321	-0.273 mmol/L Standard Error 0.290

SECONDARY outcome

Timeframe: Baseline to 14 weeks of dosing

Percentage change in 10-day percentage time spent in hyperglycaemia of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks

Outcome measures

Measure	Cotadutide 100 ug n=30 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=25 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=26 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=30 Participants Participants randomised to placebo daily
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing	-13.87 Percent Change Standard Error 3.35	-15.79 Percent Change Standard Error 3.55	-13.90 Percent Change Standard Error 3.52	-4.09 Percent Change Standard Error 3.27

SECONDARY outcome

Timeframe: Baseline to 26 weeks of dosing

Percentage change in 10-day percentage time spent in hyperglycaemia of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks

Outcome measures

Measure	Cotadutide 100 ug n=25 Participants Participants randomised to cotadutide 100 µg daily	Cotadutide 300 µg n=18 Participants Participants randomised to cotadutide 300 µg	Cotadutide 600 µg n=22 Participants Participants randomised to cotadutide 600 µg	Placebo ug n=27 Participants Participants randomised to placebo daily
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing	-18.06 Percent change Standard Error 3.33	-15.38 Percent change Standard Error 3.76	-11.91 Percent change Standard Error 3.51	-3.00 Percent change Standard Error 3.17

Adverse Events

Cotadutide 100 ug

Serious events: 5 serious events

Other events: 43 other events

Deaths: 2 deaths

Cotadutide 300 ug

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Cotadutide 600 ug

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo ug

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Semaglutide 1 mg

Serious events: 5 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cotadutide 100 ug n=52 participants at risk Participants randomised to cotadutide 100 µg daily	Cotadutide 300 ug n=49 participants at risk Participants randomised to Cotadutide 300 ug daily	Cotadutide 600 ug n=51 participants at risk Participants randomised to Cotadutide 600 ug daily	Placebo ug n=51 participants at risk Participants randomised to placebo daily	Semaglutide 1 mg n=45 participants at risk Participants randomized to semaglutide 1 mg weekly
Cardiac disorders Coronary artery disease	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Ischaemic stroke	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Psychiatric disorders Adjustment disorder with anxiety	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Renal failure	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Acute kidney injury	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Vascular disorders Hypertension	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Constipation	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Acute myocardial infarction	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Angina pectoris	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Covid-19	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Diverticulitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Pneumonia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Humerus fracture	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hypoglycaemia	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Ketosis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Psychiatric disorders Suspected suicide	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Vomiting	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Chest pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Vestibular neuronitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.

Other adverse events

Measure	Cotadutide 100 ug n=52 participants at risk Participants randomised to cotadutide 100 µg daily	Cotadutide 300 ug n=49 participants at risk Participants randomised to Cotadutide 300 ug daily	Cotadutide 600 ug n=51 participants at risk Participants randomised to Cotadutide 600 ug daily	Placebo ug n=51 participants at risk Participants randomised to placebo daily	Semaglutide 1 mg n=45 participants at risk Participants randomized to semaglutide 1 mg weekly
Investigations Amylase increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood bicarbonate decreased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood bicarbonate increased	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood calcium increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood creatinine increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood glucose increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood potassium increased	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood pressure decreased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood pressure increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Blood sodium increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Cardiac murmur	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Ejection fraction decreased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Electrocardiogram qt prolonged	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Electrocardiogram change	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Glomerular filtration rate decreased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.4% 2/45 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Lipase increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Occult blood positive	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Mitral valve incompetence	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Pedal pulse decreased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Pulmonary arterial pressure increased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Pulse absent	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Urine output increased	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Ventricular internal diameter	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Atrioventricular block second degree	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Animal bite	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Contusion	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Costal cartilage fracture	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Epicondylitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Fall	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Heat illness	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 6 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Heat stroke	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Ligament rupture	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Limb injury	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Skin pressure mark	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Skin wound	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Conduction disorder	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Vaccination complication	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Investigations Weight decreased	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	6.1% 3/49 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	9.8% 5/51 • Number of events 5 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	17.8% 8/45 • Number of events 8 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Gout	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	— 0/0 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Palpitations	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hyperglycaemia	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hyperkalaemia	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	6.7% 3/45 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hypernatraemia	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hyperuricaemia	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hypervolaemia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hypoglycaemia	25.0% 13/52 • Number of events 88 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	32.7% 16/49 • Number of events 106 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	25.5% 13/51 • Number of events 83 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	25.5% 13/51 • Number of events 148 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	8.9% 4/45 • Number of events 4 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hypophagia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Iron deficiency	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Pericardial effusion	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Arthritis	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Back pain	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	7.8% 4/51 • Number of events 4 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.4% 2/45 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Joint contracture	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Muscle spasms	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.4% 2/45 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Sinus tachycardia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal neoplasm	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma stage iii	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Akinesia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Tachycardia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Cognitive disorder	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Dizziness	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	8.2% 4/49 • Number of events 4 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Dizziness postural	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Headache	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 5 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.4% 2/45 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Lethargy	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Migraine	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Myelopathy	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Neuropathy peripheral	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Ventricular tachycardia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Polyneuropathy	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Presyncope	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Restless legs syndrome	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Sciatica	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Syncope	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Psychiatric disorders Cardiovascular somatic symptom disorder	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Psychiatric disorders Depressed mood	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Psychiatric disorders Insomnia	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Blood and lymphatic system disorders Anaemia	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Ear and labyrinth disorders Vertigo	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Psychiatric disorders Irritability	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Nocturia	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Pollakiuria	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Polyuria	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Renal mass	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Urinary hesitation	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Renal and urinary disorders Urinary incontinence	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Endocrine disorders Thyroid mass	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Reproductive system and breast disorders Breast tenderness	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Allergic cough	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.9% 1/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Cataract	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Rales	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Conjunctival haemorrhage	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Blister	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Diabetic retinopathy	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Eye haemorrhage	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Eye pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Glaucoma	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Macular oedema	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Retinal haemorrhage	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Blood and lymphatic system disorders Blood loss anaemia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Vitreous detachment	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Eye disorders Vitreous floaters	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Abdominal discomfort	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Abdominal distension	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Abdominal pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Chronic gastritis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Constipation	13.5% 7/52 • Number of events 7 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	9.8% 5/51 • Number of events 7 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	6.7% 3/45 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Diarrhoea	9.6% 5/52 • Number of events 5 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	14.3% 7/49 • Number of events 10 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	11.8% 6/51 • Number of events 9 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	7.8% 4/51 • Number of events 8 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	15.6% 7/45 • Number of events 7 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Dyspepsia	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	8.2% 4/49 • Number of events 5 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Eructation	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Faeces hard	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Flatulence	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	6.7% 3/45 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Haemorrhoids	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Large intestine polyp	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Nausea	11.5% 6/52 • Number of events 7 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	14.3% 7/49 • Number of events 9 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	27.5% 14/51 • Number of events 18 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	9.8% 5/51 • Number of events 5 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	26.7% 12/45 • Number of events 12 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Oral lichen planus	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Angina pectoris	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Toothache	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Gastrointestinal disorders Vomiting	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	6.1% 3/49 • Number of events 4 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	13.7% 7/51 • Number of events 12 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	15.6% 7/45 • Number of events 7 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Asthenia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.4% 2/45 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Chest pain	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Early satiety	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Fatigue	5.8% 3/52 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Injection site bruising	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Injection site erythema	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Injection site induration	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Injection site pain	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Angina unstable	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Injection site pruritus	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Injection site reaction	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Malaise	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Oedema	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Oedema peripheral	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Pain	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Peripheral swelling	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Puncture site haemorrhage	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Pyrexia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
General disorders Vaccination site pain	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Atrial fibrillation	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Hepatobiliary disorders Hepatomegaly	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Bronchitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Covid-19	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.4% 2/45 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Cellulitis	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Conjunctivitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Cystitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Eye infection	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Atrial flutter	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Fungal skin infection	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Gastroenteritis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Giardiasis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Localised infection	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Lower respiratory tract infection	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Nasopharyngitis	3.8% 2/52 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	6.7% 3/45 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Onychomycosis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Paronychia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Periodontitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Pneumonia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Atrioventricular block first degree	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.1% 2/49 • Number of events 4 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Rhinitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Sinusitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Tinea infection	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Tonsillitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Tooth abscess	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Upper respiratory tract infection	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Urinary tract infection	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	6.1% 3/49 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	3.9% 2/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	4.4% 2/45 • Number of events 2 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Vestibular neuronitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Vulvovaginal candidiasis	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Cardiac disorders Cardiac septal hypertrophy	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Ischaemic stroke	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Nervous system disorders Neuralgia	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Psychiatric disorders Depression	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Dermal cyst	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Lichenification	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Macule	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Rash	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Scab	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 3 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Surgical and medical procedures Meniscus removal	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Surgical and medical procedures Skin neoplasm excision	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Surgical and medical procedures Tooth extraction	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Vascular disorders Aortic stenosis	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Vascular disorders Haematoma	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Vascular disorders Hot flush	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Vascular disorders Hypertension	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/51 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Vascular disorders Hypotension	0.00% 0/52 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.0% 1/49 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	5.9% 3/51 • Number of events 4 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	11.1% 5/45 • Number of events 5 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Asymptomatic covid-19	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/45 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.
Infections and infestations Viral upper respiratory tract infection	1.9% 1/52 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/49 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	0.00% 0/51 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.	2.2% 1/45 • Number of events 1 • Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.

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

Restriction type: LTE60