Trial Outcomes & Findings for A Study of Two Doses of Dulaglutide (LY2189265) in Japanese Patients With Type 2 Diabetes (NCT NCT04809220)

Last Updated: 2024-05-22

Results Overview

HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Pre-study oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment × Time as variables.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

591 participants

Primary outcome timeframe

Baseline, Week 26

Results posted on

2024-05-22

Participant Flow

591 participants were randomized in the study. However, due to good clinical practice (GCP) compliance issues identified at one of the investigative sites, all 5 participants from that site were excluded from the study analyses.

Participant milestones

Participant milestones
Measure	Dulaglutide 1.5 Milligram (mg) Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.
Overall Study STARTED	395	196
Overall Study Exposed to at Least 1 Dose of Study Intervention (Excluding the GCP Compliance Investigative Site)	391	195
Overall Study COMPLETED	377	190
Overall Study NOT COMPLETED	18	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dulaglutide 1.5 Milligram (mg) Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.
Overall Study Adverse Event	4	0
Overall Study Death	1	0
Overall Study Lost to Follow-up	3	0
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	9	5
Overall Study Due to long-term overseas business trips	1	0

Baseline Characteristics

A Study of Two Doses of Dulaglutide (LY2189265) in Japanese Patients With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dulaglutide 1.5 mg n=391 Participants Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=195 Participants Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Total n=586 Participants Total of all reporting groups
Age, Continuous	60.10 years STANDARD_DEVIATION 10.70 • n=5 Participants	60.70 years STANDARD_DEVIATION 10.74 • n=7 Participants	60.30 years STANDARD_DEVIATION 10.71 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants	53 Participants n=7 Participants	166 Participants n=5 Participants
Sex: Female, Male Male	278 Participants n=5 Participants	142 Participants n=7 Participants	420 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	391 Participants n=5 Participants	195 Participants n=7 Participants	586 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Japan	391 Participants n=5 Participants	195 Participants n=7 Participants	586 Participants n=5 Participants
Hemoglobin A1c (HbA1c)	8.61 Percentage of HbA1c STANDARD_DEVIATION 0.62 • n=5 Participants	8.61 Percentage of HbA1c STANDARD_DEVIATION 0.60 • n=7 Participants	8.61 Percentage of HbA1c STANDARD_DEVIATION 0.61 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention and had at least one post baseline value for this analysis.

Outcome measures

Outcome measures
Measure	Dulaglutide 1.5 mg n=383 Participants Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=193 Participants Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26	-1.53 Percentage of HbA1c Standard Error 0.043	-1.25 Percentage of HbA1c Standard Error 0.060

SECONDARY outcome

Timeframe: Baseline, Week 52

HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables.

Outcome measures

Outcome measures
Measure	Dulaglutide 1.5 mg n=383 Participants Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=193 Participants Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide
Change From Baseline in HbA1c at Week 52	-1.50 Percentage of HbA1c Standard Error 0.046	-1.19 Percentage of HbA1c Standard Error 0.065

SECONDARY outcome

Timeframe: Week 52

HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The odds ratios, confidence intervals, and p-values were determined by generalized linear mixed model (GLM) with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables.

Outcome measures

Outcome measures
Measure	Dulaglutide 1.5 mg n=354 Participants Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=174 Participants Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide
Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% HbA1c ≤ 6.5%	22.88 Percentage of participants	21.26 Percentage of participants
Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% HbA1c < 7%	46.33 Percentage of participants	38.51 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

FSG is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment\*Time as variables.

Outcome measures

Outcome measures
Measure	Dulaglutide 1.5 mg n=382 Participants Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=191 Participants Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide
Change From Baseline in Fasting Serum Glucose (FSG)	-42.4 milligrams per deciliter (mg/dL) Standard Error 1.47	-33.1 milligrams per deciliter (mg/dL) Standard Error 2.09

SECONDARY outcome

Timeframe: Baseline, Week 26

SMBG 6-point profiles were measured at morning (premeal-fasting, 2-hour post meal), midday (premeal, 2-hour post meal), and evening (premeal, 2-hour post meal). LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment as variables.

Outcome measures

Outcome measures
Measure	Dulaglutide 1.5 mg n=362 Participants Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=185 Participants Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide
Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) Morning premeal-fasting	-45.6 mg/dL Standard Error 1.33	-38.4 mg/dL Standard Error 1.86
Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) Morning 2-hour post meal	-70.6 mg/dL Standard Error 2.42	-60.5 mg/dL Standard Error 3.39
Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) Midday premeal	-55.3 mg/dL Standard Error 1.77	-47.0 mg/dL Standard Error 2.47
Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) Midday 2-hour post meal	-73.7 mg/dL Standard Error 2.37	-61.2 mg/dL Standard Error 3.32
Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) Evening premeal	-50.3 mg/dL Standard Error 1.60	-46.4 mg/dL Standard Error 2.24
Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) Evening 2-hour post meal	-61.1 mg/dL Standard Error 2.27	-49.8 mg/dL Standard Error 3.18

SECONDARY outcome

Timeframe: Baseline, Week 52

LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment\*Time as variables.

Outcome measures

Outcome measures
Measure	Dulaglutide 1.5 mg n=383 Participants Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=193 Participants Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide
Change From Baseline in Body Weight	-0.5 kilogram (kg) Standard Error 0.14	-0.2 kilogram (kg) Standard Error 0.19

Adverse Events

Dulaglutide 1.5 mg

Serious events: 15 serious events

Other events: 298 other events

Deaths: 1 deaths

Dulaglutide 0.75 mg

Serious events: 7 serious events

Other events: 143 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Dulaglutide 1.5 mg n=391 participants at risk Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.	Dulaglutide 0.75 mg n=195 participants at risk Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide.
Cardiac disorders Acute myocardial infarction	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Angina pectoris	0.00% 0/391 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.51% 1/195 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Cardiac failure congestive	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Mitral valve incompetence	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Eye disorders Retinal haemorrhage	0.00% 0/391 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.51% 1/195 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Eye disorders Vitreous haemorrhage	0.00% 0/391 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.51% 1/195 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Colitis ischaemic	0.00% 0/391 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.51% 1/195 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/391 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.51% 1/195 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Large intestine polyp	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Covid-19	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Covid-19 pneumonia	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Osteomyelitis	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Hand fracture	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Humerus fracture	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Synovial cyst	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma stage 0	0.88% 1/113 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/53 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/391 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.51% 1/195 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/391 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.51% 1/195 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Brain stem haemorrhage	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Cerebral infarction	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Dizziness	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Lateral medullary syndrome	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.26% 1/391 • Number of events 1 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Baseline to Week 56. All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.