Trial Outcomes & Findings for Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Alone (NCT NCT01512108)

Last Updated: 2017-12-18

Results Overview

Adverse events were defined as events occurring after administration of trial product and no later than 7 days after last day of treatment. Severe AEs: considerable interference with subject's daily activities. Moderate AEs: Marked symptoms, moderate interference with the subject's daily activities. Mild AEs: No or transient symptoms, no interference with the subject's daily activities. Serious AEs: AEs that resulted in any of the following: death, a life-threatening experience, hospitalization/prolongation of existing hospitalization, persistent/significant disability, and congenital anomaly.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

363 participants

Primary outcome timeframe

Week 0 to Week 52 + 7 days

Results posted on

2017-12-18

Participant Flow

The trial was conducted at 36 sites in Japan.

Participant milestones

Participant milestones
Measure	Liraglutide 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Overall Study STARTED	243	120
Overall Study Exposed	240	120
Overall Study COMPLETED	221	111
Overall Study NOT COMPLETED	22	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Liraglutide 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Overall Study Adverse Event	9	4
Overall Study Protocol Violation	1	2
Overall Study Withdrawal Criteria	1	0
Overall Study Unclassified	11	3

Baseline Characteristics

Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Alone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Liraglutide 0.9 mg/Day n=240 Participants Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD n=120 Participants Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.	Total n=360 Participants Total of all reporting groups
Age, Continuous	59.6 years STANDARD_DEVIATION 11.6 • n=5 Participants	59.2 years STANDARD_DEVIATION 10.2 • n=7 Participants	59.5 years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	40 Participants n=7 Participants	98 Participants n=5 Participants
Sex: Female, Male Male	182 Participants n=5 Participants	80 Participants n=7 Participants	262 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=7 Participants	8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants
Fasting plasma glucose (FPG)	8.68 mmol/L STANDARD_DEVIATION 1.61 • n=5 Participants	8.96 mmol/L STANDARD_DEVIATION 1.82 • n=7 Participants	8.77 mmol/L STANDARD_DEVIATION 1.69 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0 to Week 52 + 7 days

Population: Safety analysis set included all subjects who received at least one dose of the trial product.

Outcome measures

Outcome measures
Measure	Liraglutide 0.9 mg/Day n=240 Participants Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD n=120 Participants Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Incidence of Treatment Emergent Adverse Events (AEs) All AEs	361 Events/100 years of patient exposure	331 Events/100 years of patient exposure
Incidence of Treatment Emergent Adverse Events (AEs) Mild AEs	345 Events/100 years of patient exposure	321 Events/100 years of patient exposure
Incidence of Treatment Emergent Adverse Events (AEs) Moderate AEs	14 Events/100 years of patient exposure	9 Events/100 years of patient exposure
Incidence of Treatment Emergent Adverse Events (AEs) Severe AEs	2 Events/100 years of patient exposure	2 Events/100 years of patient exposure
Incidence of Treatment Emergent Adverse Events (AEs) Serious AEs	5 Events/100 years of patient exposure	9 Events/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 52

Population: Safety analysis set includes all subjects who received at least one dose of the trial product.

Confirmed hypoglycaemic episodes consisted of the pool of episodes of severe hypoglycaemia as well as minor hypoglycaemic episodes \[An episode with symptoms consistent with hypoglycaemia with confirmation by plasma glucose \<3.1 mmol/L (56 mg/dL) or full blood glucose \<2.8 mmol/L (50 mg/dL) and which is handled by the subject himself or herself or any asymptomatic PG value \<3.1 mmol/L (56 mg/dL) or full blood glucose value \<2.8 mmol/L (50 mg/dL)\] with a confirmed plasma glucose value of less than 3.1 mmol/L (56 mg/dL).

Outcome measures

Outcome measures
Measure	Liraglutide 0.9 mg/Day n=240 Participants Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD n=120 Participants Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Number of Confirmed Hypoglycaemic Episodes	7 episodes	2 episodes

SECONDARY outcome

Timeframe: Week 0, week 52

Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products and missing data were imputed using last observation carried forward (LOCF). One subject did not contribute to the statistical analysis at Week 52.

Estimated mean change in HbA1c from baseline after 52 Weeks of treatment

Outcome measures

Outcome measures
Measure	Liraglutide 0.9 mg/Day n=239 Participants Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD n=120 Participants Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Change in HbA1c From Baseline to Week 52	-1.21 percentage of glycosylated haemoglobin Standard Error 0.05	-0.94 percentage of glycosylated haemoglobin Standard Error 0.07

SECONDARY outcome

Timeframe: Week 0, week 52

Estimated mean change from baseline in FPG after 52 Weeks of treatment

Outcome measures

Outcome measures
Measure	Liraglutide 0.9 mg/Day n=239 Participants Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD n=120 Participants Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Change in FPG From Baseline to Week 52	-1.55 mmol/L Standard Error 0.09	-1.24 mmol/L Standard Error 0.12

Adverse Events

Liraglutide 0.9 mg/Day

Serious events: 11 serious events

Other events: 161 other events

Deaths: 0 deaths

Additional OAD

Serious events: 10 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Liraglutide 0.9 mg/Day n=240 participants at risk Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD n=120 participants at risk Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Eye disorders Cataract	3.3% 8/240 • Number of events 8 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	6.7% 8/120 • Number of events 8 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Eye disorders Diabetic retinopathy	8.8% 21/240 • Number of events 22 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	13.3% 16/120 • Number of events 16 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Gastrointestinal disorders Abdominal discomfort	7.9% 19/240 • Number of events 21 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Gastrointestinal disorders Constipation	18.3% 44/240 • Number of events 48 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	10.0% 12/120 • Number of events 13 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Gastrointestinal disorders Dental caries	2.9% 7/240 • Number of events 7 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	5.0% 6/120 • Number of events 6 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Gastrointestinal disorders Diarrhoea	8.3% 20/240 • Number of events 25 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	7.5% 9/120 • Number of events 10 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Gastrointestinal disorders Nausea	12.9% 31/240 • Number of events 33 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	3.3% 4/120 • Number of events 4 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Infections and infestations Influenza	3.3% 8/240 • Number of events 8 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	5.0% 6/120 • Number of events 6 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Infections and infestations Nasopharyngitis	37.1% 89/240 • Number of events 135 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	39.2% 47/120 • Number of events 85 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Musculoskeletal and connective tissue disorders Back pain	5.4% 13/240 • Number of events 14 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	2.5% 3/120 • Number of events 3 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Nervous system disorders Headache	5.0% 12/240 • Number of events 14 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	3.3% 4/120 • Number of events 4 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Novo Nordisk maintains the right to be informed of any Investigator plans for publication and review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Novo Nordisk reserves the right to prior review of such publications and ask for delay of publication of individual site results until after the primary manuscript is accepted for publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Liraglutide 0.9 mg/Day n=240 participants at risk Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.	Additional OAD n=120 participants at risk Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual's glycaemic control by the investigator as per Japanese labelling.
Cardiac disorders Arteriosclerosis coronary artery	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Cardiac disorders Cardiac failure	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Ear and labyrinth disorders Deafness neurosensory	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Eye disorders Diabetic retinopathy	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Gastrointestinal disorders Enterocolitis	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Gastrointestinal disorders Inguinal hernia	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
General disorders Chest pain	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Infections and infestations Meningitis herpes	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Injury, poisoning and procedural complications Fall	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer stage II	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine carcinoma	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma unspecified stage II	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage II	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Nervous system disorders Cerebral infarction	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.42% 1/240 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.00% 0/120 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.
Surgical and medical procedures Limb operation	0.00% 0/240 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.	0.83% 1/120 • Number of events 1 • Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit. Safety analysis set included all subjects who received at least one dose of the trial product.