Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes (NCT NCT03235050)

NCT ID: NCT03235050

Last Updated: 2020-08-17

Results Overview

To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 834 participants
• Primary outcome timeframe: From baseline to 14 weeks
• Results posted on: 2020-08-17

Participant Flow

Participant milestones

Measure	Placebo Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Liraglutide Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg MEDI0382(cotadutide) low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg MEDI0382(cotadutide) mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg MEDI0382(cotadutide) high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Overall Study STARTED	112	110	100	256	256
Overall Study COMPLETED	108	105	96	242	245
Overall Study NOT COMPLETED	4	5	4	14	11

Reasons for withdrawal

Measure	Placebo Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Liraglutide Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg MEDI0382(cotadutide) low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg MEDI0382(cotadutide) mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg MEDI0382(cotadutide) high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Overall Study Adverse Event	0	0	1	4	1
Overall Study Death	0	0	0	2	1
Overall Study Lost to Follow-up	1	2	1	2	0
Overall Study Withdrawal by Subject	3	2	2	5	7
Overall Study Other reasons	0	1	0	1	2

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Liraglutide n=110 Participants Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Total n=834 Participants Total of all reporting groups
Age, Continuous	57.3 Years STANDARD_DEVIATION 9.5 • n=5 Participants	55.5 Years STANDARD_DEVIATION 9.8 • n=7 Participants	57.6 Years STANDARD_DEVIATION 9.9 • n=5 Participants	57.3 Years STANDARD_DEVIATION 9.9 • n=4 Participants	56.3 Years STANDARD_DEVIATION 10.2 • n=21 Participants	56.8 Years STANDARD_DEVIATION 9.9 • n=10 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	60 Participants n=7 Participants	57 Participants n=5 Participants	147 Participants n=4 Participants	129 Participants n=21 Participants	448 Participants n=10 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	50 Participants n=7 Participants	43 Participants n=5 Participants	109 Participants n=4 Participants	127 Participants n=21 Participants	386 Participants n=10 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants	0 Participants n=21 Participants	11 Participants n=10 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	6 Participants n=10 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	10 Participants n=10 Participants
Race/Ethnicity, Customized White	107 Participants n=5 Participants	103 Participants n=7 Participants	99 Participants n=5 Participants	245 Participants n=4 Participants	252 Participants n=21 Participants	806 Participants n=10 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants

PRIMARY outcome

Timeframe: From baseline to 14 weeks

Population: ITT population

To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Change in HbA1c	-0.18 percentage Interval -0.34 to -0.02	-1.01 percentage Interval -1.18 to -0.84	-1.22 percentage Interval -1.33 to -1.11	-1.09 percentage Interval -1.2 to -0.98

PRIMARY outcome

Timeframe: From baseline to 14 weeks

Population: ITT population

To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Percent Change in Body Weight	-0.70 percentage Interval -1.44 to 0.04	-2.70 percentage Interval -3.49 to -1.91	-3.47 percentage Interval -3.95 to -2.98	-4.33 percentage Interval -4.82 to -3.84

SECONDARY outcome

Timeframe: from baseline to 26 weeks and 54 weeks

Population: ITT population

To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Change in HbA1c from baseline to 26 weeks	-0.40 percentage Interval -0.58 to -0.22	-1.06 percentage Interval -1.25 to -0.87	-1.22 percentage Interval -1.34 to -1.1	-1.12 percentage Interval -1.24 to -1.0
Change in HbA1c from baseline to 54 weeks	-0.44 percentage Interval -0.63 to -0.24	-0.96 percentage Interval -1.16 to -0.75	-1.06 percentage Interval -1.19 to -0.93	-1.01 percentage Interval -1.14 to -0.88

SECONDARY outcome

Timeframe: after 14, 26, and 54 weeks

Population: Intent-to-Treat (ITT) population

To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of participants achieving an HbA1c target of <7% versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Percentage of Participants Achieving an HbA1c Target < 7.0% after 14 weeks	19 Participants	50 Participants	143 Participants	143 Participants
Percentage of Participants Achieving an HbA1c Target < 7.0% after 26 weeks	25 Participants	48 Participants	139 Participants	143 Participants
Percentage of Participants Achieving an HbA1c Target < 7.0% after 54 weeks	23 Participants	52 Participants	125 Participants	128 Participants

SECONDARY outcome

Timeframe: from baseline to 26 weeks and 54 weeks

Population: ITT population

To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Percent Change in Body Weight from baseline to 26 weeks	-1.14 percentage Interval -1.99 to -0.29	-3.23 percentage Interval -4.13 to -2.32	-3.94 percentage Interval -4.51 to -3.38	-4.60 percentage Interval -5.17 to -4.04
Percent Change in Body Weight from baseline to 54 weeks	-0.84 percentage Interval -1.82 to 0.14	-3.27 percentage Interval -4.32 to -2.22	-3.08 percentage Interval -3.73 to -2.43	-4.16 percentage Interval -4.81 to -3.5

SECONDARY outcome

Timeframe: from baseline to 14 weeks, 26 weeks and 54 weeks

Population: ITT population

To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Absolute Change in Body Weight from baseline to 14 weeks	-0.71 kg Interval -1.44 to 0.03	-2.66 kg Interval -3.45 to -1.87	-3.45 kg Interval -3.94 to -2.97	-4.42 kg Interval -4.91 to -3.93
Absolute Change in Body Weight from baseline to 26 weeks	-1.20 kg Interval -2.06 to -0.34	-3.20 kg Interval -4.13 to -2.28	-3.94 kg Interval -4.52 to -3.37	-4.75 kg Interval -5.33 to -4.18
Absolute Change in Body Weight from baseline to 54 weeks	-0.94 kg Interval -1.94 to 0.07	-3.20 kg Interval -4.28 to -2.12	-3.09 kg Interval -3.77 to -2.42	-4.35 kg Interval -5.03 to -3.68

SECONDARY outcome

Timeframe: from baseline to 14 weeks, 26 weeks and 54 weeks

Population: ITT population

To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily

Outcome measures

Measure	Placebo n=110 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Percent Change in Body Weight Versus Active Comparator Percent change at 14 weeks	-3.40 percentage Interval -4.14 to -2.65	-2.70 percentage Interval -3.49 to -1.91	-3.47 percentage Interval -3.95 to -2.98	-4.33 percentage Interval -4.82 to -3.84
Percent Change in Body Weight Versus Active Comparator Percent change at 26 weeks	-4.12 percentage Interval -4.98 to -3.27	-3.23 percentage Interval -4.13 to -2.32	-3.94 percentage Interval -4.51 to -3.38	-4.60 percentage Interval -5.17 to -4.04
Percent Change in Body Weight Versus Active Comparator Percent change at 54 weeks	-3.20 percentage Interval -4.19 to -2.21	-3.27 percentage Interval -4.32 to -2.22	-3.08 percentage Interval -3.73 to -2.43	-4.16 percentage Interval -4.81 to -3.5

SECONDARY outcome

Timeframe: from baseline to 14 weeks, 26 weeks and 54 weeks

Population: ITT population

To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily

Outcome measures

Measure	Placebo n=110 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Absolute Change in Body Weight Versus Active Comparator Absolute change at 14 weeks	-3.25 kg Interval -4.0 to -2.51	-2.66 kg Interval -3.45 to -1.87	-3.45 kg Interval -3.94 to -2.97	-4.42 kg Interval -4.91 to -3.93
Absolute Change in Body Weight Versus Active Comparator Absolute change at 26 weeks	-3.90 kg Interval -4.77 to -3.03	-3.20 kg Interval -4.13 to -2.28	-3.94 kg Interval -4.52 to -3.37	-4.75 kg Interval -5.33 to -4.18
Absolute Change in Body Weight Versus Active Comparator Absolute change at 54 weeks	-2.94 kg Interval -3.96 to -1.92	-3.20 kg Interval -4.28 to -2.12	-3.09 kg Interval -3.77 to -2.42	-4.35 kg Interval -5.03 to -3.68

SECONDARY outcome

Timeframe: after 14 weeks, 26 weeks and 54 weeks

Population: ITT population

To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of subjects achieving weight loss of ≥5% and ≥10% versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Percentage of Participants Achieving Weight Loss of ≥5% and ≥10% Participants with weight loss ≥5% at Wk 14 (LOCF)	3 Participants	18 Participants	65 Participants	92 Participants
Percentage of Participants Achieving Weight Loss of ≥5% and ≥10% Participants with weight loss ≥5% at Wk 26 (LOCF)	11 Participants	28 Participants	76 Participants	110 Participants
Percentage of Participants Achieving Weight Loss of ≥5% and ≥10% Participants with weight loss ≥5% at Wk 54 (LOCF)	14 Participants	34 Participants	71 Participants	98 Participants
Percentage of Participants Achieving Weight Loss of ≥5% and ≥10% Participants with weight loss ≥10% at Wk 14 (LOCF)	0 Participants	6 Participants	15 Participants	20 Participants
Percentage of Participants Achieving Weight Loss of ≥5% and ≥10% Participants with weight loss ≥10% at Wk 26 (LOCF)	1 Participants	7 Participants	28 Participants	27 Participants
Percentage of Participants Achieving Weight Loss of ≥5% and ≥10% Participants with weight loss ≥10% at Wk 54 (LOCF)	2 Participants	11 Participants	21 Participants	32 Participants

SECONDARY outcome

Timeframe: at 14 weeks, 26 weeks and 54 weeks

Population: ITT population

To assess the effect of 100, 200, and 300 μg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control received rescue medication at 14 wks	11 Participants	1 Participants	3 Participants	2 Participants
Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control received rescue medication at 26 wks	20 Participants	3 Participants	8 Participants	6 Participants
Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control received rescue medication at 54 wks	34 Participants	10 Participants	26 Participants	24 Participants
Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control discontinued study IP at 14 wks	2 Participants	0 Participants	1 Participants	0 Participants
Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control discontinued study IP at 26 wks	4 Participants	1 Participants	2 Participants	0 Participants
Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control discontinued study IP at 54 wks	4 Participants	1 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54

Population: Per-protocol population

To characterise the PK profile of 100, 200, and 300 μg of cotadutide

Outcome measures

Measure	Placebo Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 1	—	2.68 ng/mL Standard Deviation 1.27	2.76 ng/mL Standard Deviation 1.88	2.77 ng/mL Standard Deviation 1.84
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 2	—	2.66 ng/mL Standard Deviation 1.61	5.13 ng/mL Standard Deviation 3.23	5.18 ng/mL Standard Deviation 3.05
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 6	—	2.75 ng/mL Standard Deviation 1.44	5.20 ng/mL Standard Deviation 3.57	7.77 ng/mL Standard Deviation 4.88
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 10	—	3.18 ng/mL Standard Deviation 2.26	5.74 ng/mL Standard Deviation 4.23	8.23 ng/mL Standard Deviation 4.31
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 14	—	3.79 ng/mL Standard Deviation 4.05	6.50 ng/mL Standard Deviation 5.26	9.71 ng/mL Standard Deviation 7.64
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 18	—	4.58 ng/mL Standard Deviation 5.04	7.43 ng/mL Standard Deviation 6.43	10.8 ng/mL Standard Deviation 7.95
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 22	—	4.63 ng/mL Standard Deviation 4.28	8.07 ng/mL Standard Deviation 7.01	11.5 ng/mL Standard Deviation 9.77
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 26	—	4.39 ng/mL Standard Deviation 3.33	8.12 ng/mL Standard Deviation 7.31	12.9 ng/mL Standard Deviation 12.1
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) Week 54	—	4.58 ng/mL Standard Deviation 3.89	8.99 ng/mL Standard Deviation 9.22	13.2 ng/mL Standard Deviation 14.3

SECONDARY outcome

Timeframe: Baseline through 54-week treatment period and 28-day follow-up

Population: As-treated population

To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants) ADA positive at baseline	1 Participants	1 Participants	0 Participants	0 Participants
Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants) ADA incidence	3 Participants	55 Participants	152 Participants	155 Participants
Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants) ADA positive post-baseline	3 Participants	54 Participants	152 Participants	155 Participants

SECONDARY outcome

Timeframe: Baseline through 54-week treatment period and 28-day follow-up

Population: As-treated population

To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide

Outcome measures

Measure	Placebo n=112 Participants Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 Participants MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 Participants MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 Participants MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants ADA positive at baseline, median titer	5.0 titer Interval 5.0 to 5.0	5.0 titer Interval 5.0 to 5.0	0 titer Interval 0.0 to 0.0	0 titer Interval 0.0 to 0.0
Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants ADA incidence, median of maximum titer	5.0 titer Interval 5.0 to 20.0	20.0 titer Interval 5.0 to 2560.0	20.0 titer Interval 5.0 to 640.0	20.0 titer Interval 5.0 to 5120.0
Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants ADA positive post-baseline, median of max. titer	5.0 titer Interval 5.0 to 20.0	20.0 titer Interval 5.0 to 2560.0	20.0 titer Interval 5.0 to 640.0	20.0 titer Interval 5.0 to 5120.0

Adverse Events

Placebo

Serious events: 12 serious events

Other events: 45 other events

Deaths: 0 deaths

Liraglutide

Serious events: 8 serious events

Other events: 36 other events

Deaths: 0 deaths

MEDI0382 100 mcg

Serious events: 12 serious events

Other events: 51 other events

Deaths: 0 deaths

MEDI0382 200 mcg

Serious events: 33 serious events

Other events: 159 other events

Deaths: 2 deaths

MEDI0382 300 mcg

Serious events: 20 serious events

Other events: 164 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=112 participants at risk Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Liraglutide n=110 participants at risk Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 participants at risk MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 participants at risk MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 participants at risk MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Cardiac disorders Aortic valve stenosis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Atrial fibrillation	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Atrial flutter	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Atrioventricular block complete	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Acute myocardial infarction	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Angina pectoris	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.78% 2/256 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Angina unstable	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.78% 2/256 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Bradycardia	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Cardiac failure chronic	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Cardiac failure congestive	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Coronary artery disease	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Myocardial infarction	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Myocardial ischaemia	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Cardiac disorders Silent myocardial infarction	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Eye disorders Retinal detachment	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Eye disorders Retinal tear	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Abdominal pain	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Colitis ulcerative	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Enterocutaneous fistula	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Gastric polyps	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Hiatus hernia	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Inguinal hernia	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Megacolon	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Retroperitoneal haematoma	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
General disorders Impaired healing	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Hepatobiliary disorders Cholelithiasis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.78% 2/256 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Hepatobiliary disorders Gallbladder polyp	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Acarodermatitis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Appendicitis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Bacterial infection	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Cellulitis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Chronic sinusitis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Erysipelas	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Gastroenteritis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Otitis media acute	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Pneumonia	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	2.0% 2/100 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Postoperative wound infection	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Pyelonephritis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Pyelonephritis chronic	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Skin infection	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Urinary tract infection	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Anastomotic leak	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Arterial bypass occlusion	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Concussion	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Humerus fracture	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Limb injury	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Post procedural fistula	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Spinal column injury	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Musculoskeletal and connective tissue disorders Arthrofibrosis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Musculoskeletal and connective tissue disorders Haematoma muscle	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Musculoskeletal and connective tissue disorders Meniscal degeneration	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.2% 3/256 • Number of events 3 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage unspecified	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Triple negative breast cancer	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Cerebrovascular disorder	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Diabetic neuropathy	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Haemorrhagic stroke	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Ischaemic stroke	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.78% 2/256 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Transient ischaemic attack	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Vertigo cns origin	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Renal and urinary disorders Chronic kidney disease	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Renal and urinary disorders Nephrolithiasis	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Renal and urinary disorders Perinephritis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Renal and urinary disorders Prerenal failure	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Renal and urinary disorders Urinary tract disorder	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Reproductive system and breast disorders Acquired phimosis	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Reproductive system and breast disorders Uterine prolapse	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Respiratory, thoracic and mediastinal disorders Vocal cord dysfunction	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Vascular disorders Hypertension	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.39% 1/256 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Vascular disorders Hypertensive crisis	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/100 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.78% 2/256 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/256 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.

Other adverse events

Measure	Placebo n=112 participants at risk Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Liraglutide n=110 participants at risk Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 100 mcg n=100 participants at risk MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 200 mcg n=256 participants at risk MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	MEDI0382 300 mcg n=256 participants at risk MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Gastrointestinal disorders Eructation	0.00% 0/112 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	2.0% 2/100 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	5.5% 14/256 • Number of events 17 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	4.7% 12/256 • Number of events 15 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Nausea	10.7% 12/112 • Number of events 13 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	15.5% 17/110 • Number of events 21 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	23.0% 23/100 • Number of events 28 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	33.2% 85/256 • Number of events 115 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	41.0% 105/256 • Number of events 143 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Vomiting	4.5% 5/112 • Number of events 6 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	2.7% 3/110 • Number of events 3 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	10.0% 10/100 • Number of events 12 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	19.9% 51/256 • Number of events 66 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	16.8% 43/256 • Number of events 58 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Nasopharyngitis	13.4% 15/112 • Number of events 19 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	10.0% 11/110 • Number of events 13 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	11.0% 11/100 • Number of events 13 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	8.6% 22/256 • Number of events 28 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	10.9% 28/256 • Number of events 44 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Constipation	1.8% 2/112 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.8% 2/110 • Number of events 3 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	3.9% 10/256 • Number of events 10 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	5.1% 13/256 • Number of events 14 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Diarrhoea	8.9% 10/112 • Number of events 10 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	3.6% 4/110 • Number of events 7 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	13.0% 13/100 • Number of events 15 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	19.1% 49/256 • Number of events 68 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	10.9% 28/256 • Number of events 40 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Gastrointestinal disorders Dyspepsia	1.8% 2/112 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	2.7% 3/110 • Number of events 3 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	7.0% 7/100 • Number of events 13 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	7.4% 19/256 • Number of events 26 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	10.9% 28/256 • Number of events 38 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Respiratory tract infection viral	2.7% 3/112 • Number of events 3 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.0% 1/100 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	5.1% 13/256 • Number of events 15 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	2.7% 7/256 • Number of events 8 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Infections and infestations Urinary tract infection	5.4% 6/112 • Number of events 6 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.8% 2/110 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	3.0% 3/100 • Number of events 4 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	5.1% 13/256 • Number of events 17 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	2.7% 7/256 • Number of events 9 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Metabolism and nutrition disorders Decreased appetite	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.91% 1/110 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	3.0% 3/100 • Number of events 3 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	4.7% 12/256 • Number of events 12 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	5.5% 14/256 • Number of events 14 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Musculoskeletal and connective tissue disorders Back pain	5.4% 6/112 • Number of events 6 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	1.8% 2/110 • Number of events 2 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	8.0% 8/100 • Number of events 8 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	3.5% 9/256 • Number of events 12 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	3.5% 9/256 • Number of events 9 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Dizziness	2.7% 3/112 • Number of events 3 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	0.00% 0/110 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	4.0% 4/100 • Number of events 5 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	4.3% 11/256 • Number of events 12 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	5.9% 15/256 • Number of events 19 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Nervous system disorders Headache	0.89% 1/112 • Number of events 1 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	4.5% 5/110 • Number of events 5 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	3.0% 3/100 • Number of events 4 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	5.9% 15/256 • Number of events 18 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.	7.4% 19/256 • Number of events 23 • Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.

Additional Information

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Phone: 1-877-240-9479

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Results disclosure agreements

• Principal investigator is a sponsor employee The Principal Investigator shall provide AstraZeneca with copies of any materials relating to the Study, the Study Documentation, or the Developed Technologies that either Party intends to publish (or submit for publication) or make any presentations relating to, at least 60 days in advance of publication, submission or presentation.
• Publication restrictions are in place

Restriction type: OTHER