Trial Outcomes & Findings for A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes on Metformin With or Without Sulfonylurea (SURPASS-AP-Combo) (NCT NCT04093752)

Last Updated: 2023-01-06

Results Overview

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily 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 covariates Baseline + Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus Sulfonylurea (SU)) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

917 participants

Primary outcome timeframe

Baseline, Week 40

Results posted on

2023-01-06

Participant Flow

Participant milestones

Participant milestones
Measure	5 mg Tirzepatide Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week (QW).	10 mg Tirzepatide Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine Participants received insulin glargine administered once daily (QD) SC. The starting dose of insulin glargine was 6 Insulin Units (IU)/day at bedtime, titrated to a fasting blood glucose (FBG) between 72-100 milligrams per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm.
Overall Study STARTED	230	228	229	230
Overall Study Received At Least One Dose of Study Drug	230	228	229	220
Overall Study COMPLETED	213	201	200	201
Overall Study NOT COMPLETED	17	27	29	29

Reasons for withdrawal

Reasons for withdrawal
Measure	5 mg Tirzepatide Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week (QW).	10 mg Tirzepatide Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine Participants received insulin glargine administered once daily (QD) SC. The starting dose of insulin glargine was 6 Insulin Units (IU)/day at bedtime, titrated to a fasting blood glucose (FBG) between 72-100 milligrams per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm.
Overall Study Adverse Event	7	19	18	4
Overall Study Withdrawal by Subject	6	6	8	20
Overall Study Lost to Follow-up	2	1	1	1
Overall Study Death	0	0	1	2
Overall Study Participant Could Not Continue Due to Work Related Reasons	0	1	0	1
Overall Study Covid 19	0	0	0	1
Overall Study Participant Thought there were Too Many Adverse Events	0	0	1	0
Overall Study Participant was Reluctant to Follow-up	1	0	0	0
Overall Study Participant Did Not Come for the Visit	1	0	0	0

Baseline Characteristics

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes on Metformin With or Without Sulfonylurea (SURPASS-AP-Combo)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5 mg Tirzepatide n=230 Participants Participants received 5 mg tirzepatide administered SC QW.	10 mg Tirzepatide n=228 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=229 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=220 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Total n=907 Participants Total of all reporting groups
Age, Continuous	53.10 years STANDARD_DEVIATION 11.25 • n=5 Participants	53.50 years STANDARD_DEVIATION 11.14 • n=7 Participants	54.30 years STANDARD_DEVIATION 11.65 • n=5 Participants	55.60 years STANDARD_DEVIATION 11.40 • n=4 Participants	54.10 years STANDARD_DEVIATION 11.38 • n=21 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	102 Participants n=7 Participants	100 Participants n=5 Participants	102 Participants n=4 Participants	400 Participants n=21 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	126 Participants n=7 Participants	129 Participants n=5 Participants	118 Participants n=4 Participants	507 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	230 Participants n=5 Participants	228 Participants n=7 Participants	229 Participants n=5 Participants	220 Participants n=4 Participants	907 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	225 Participants n=5 Participants	225 Participants n=7 Participants	226 Participants n=5 Participants	216 Participants n=4 Participants	892 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Australia	5 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	15 participants n=21 Participants
Region of Enrollment China	190 participants n=5 Participants	192 participants n=7 Participants	190 participants n=5 Participants	184 participants n=4 Participants	756 participants n=21 Participants
Region of Enrollment India	9 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants	7 participants n=4 Participants	32 participants n=21 Participants
Region of Enrollment South Korea	26 participants n=5 Participants	26 participants n=7 Participants	27 participants n=5 Participants	25 participants n=4 Participants	104 participants n=21 Participants
Hemoglobin A1c (HbA1c)	8.77 Percentage of HbA1c STANDARD_DEVIATION 0.976 • n=5 Participants	8.70 Percentage of HbA1c STANDARD_DEVIATION 0.955 • n=7 Participants	8.67 Percentage of HbA1c STANDARD_DEVIATION 0.960 • n=5 Participants	8.68 Percentage of HbA1c STANDARD_DEVIATION 0.934 • n=4 Participants	8.71 Percentage of HbA1c STANDARD_DEVIATION 0.956 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 40

Population: All randomized participants belonging to the 10 mg, 15 mg Tirzepatide and Insulin Glargine arms who received at least one dose of study drug, had a baseline and at least one post-baseline value, excluding data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date + 7 days).

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=194 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=193 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=193 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Mean Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)	-2.44 Percentage of HbA1c Standard Error 0.073	-2.49 Percentage of HbA1c Standard Error 0.072	-0.95 Percentage of HbA1c Standard Error 0.073	—

SECONDARY outcome

Timeframe: Baseline, Week 40

Population: All randomized participants belonging to the 5 mg Tirzepatide and Insulin Glargine arms who received at least one dose of study drug, had a baseline and at least one post-baseline value, excluding data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date + 7 days).

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with covariates Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=211 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=193 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Mean Change From Baseline in HbA1c (5 mg)	-2.24 Percentage of HbA1c Standard Error 0.070	-0.95 Percentage of HbA1c Standard Error 0.073	—	—

SECONDARY outcome

Timeframe: Baseline, Week 40

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline value, excluding data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date + 7 days).

LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=211 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=194 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=193 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=194 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Mean Change From Baseline in Body Weight	-5.0 kilograms (kg) Standard Error 0.32	-7.0 kilograms (kg) Standard Error 0.33	-7.2 kilograms (kg) Standard Error 0.33	1.5 kilograms (kg) Standard Error 0.33

SECONDARY outcome

Timeframe: Week 40

Population: All randomized participants who received at least one dose of study drug and had a baseline and at least one post-baseline value, excluding data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date + 7 days).

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=228 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=222 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=224 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=215 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Percentage of Participants Achieving an HbA1c Target Value of <7.0%	75.44 Percentage of participants	86.04 Percentage of participants	84.38 Percentage of participants	23.72 Percentage of participants

SECONDARY outcome

Timeframe: Week 40

HbA1c is the glycosylated fraction of hemoglobin A. Imputed data includes observed value and imputed value if endpoint measure is missing.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=228 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=222 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=224 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=215 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Percentage of Participants Achieving an HbA1c Target Value of <5.7%	14.91 Percentage of participants	20.72 Percentage of participants	27.68 Percentage of participants	0.00 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 40

Population: All randomized participants who had received at least one dose of study drug, had a baseline and at least one post-baseline value, excluding data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date + 7 days).

Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=206 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=193 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=192 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=194 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Mean Change From Baseline in Fasting Serum Glucose	-58.6 milligrams per deciliter (mg/dL) Standard Error 2.13	-66.2 milligrams per deciliter (mg/dL) Standard Error 2.19	-64.8 milligrams per deciliter (mg/dL) Standard Error 2.19	-46.2 milligrams per deciliter (mg/dL) Standard Error 2.19

SECONDARY outcome

Timeframe: Baseline, Week 40

Population: All randomized participants who have received at least one dose of study drug, had a baseline and at least one post-baseline value, excluding data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date + 7 days).

The SMBG data was collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post-meal, Midday Premeal, Midday 2-hour Post-meal, Evening Premeal, Evening 2-hour Post-meal and Bedtime. LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=204 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=193 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=186 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=188 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Mean Change in Daily Glucose Average From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values	-77.0 milligrams per deciliter (mg/dL) Standard Error 2.09	-83.4 milligrams per deciliter (mg/dL) Standard Error 2.16	-84.6 milligrams per deciliter (mg/dL) Standard Error 2.18	-42.8 milligrams per deciliter (mg/dL) Standard Error 2.18

SECONDARY outcome

Timeframe: Week 40

Population: All randomized participants who received at least one dose of study drug, had a baseline and had at least one post-baseline value, excluding data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date + 7 days).

Imputed data includes observed value and imputed value if endpoint measure is missing.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=228 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=222 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=224 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=215 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Percentage of Participants Who Achieved Weight Loss ≥5%	55.70 Percentage of participants	71.62 Percentage of participants	74.11 Percentage of participants	5.58 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 40

DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 40 or early termination. The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures with Baseline + Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline OAM Use (Met, Met plus SU) + Treatment (Type III sum of squares) as covariates.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=212 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=200 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=195 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=196 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score Hyperglycemia	-1.8 Units on a scale Standard Error 0.12	-2.1 Units on a scale Standard Error 0.12	-2.0 Units on a scale Standard Error 0.12	-1.3 Units on a scale Standard Error 0.12
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score Hypoglycemia	-1.9 Units on a scale Standard Error 0.11	-1.9 Units on a scale Standard Error 0.12	-2.0 Units on a scale Standard Error 0.12	-1.8 Units on a scale Standard Error 0.12
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score Treatment Satisfaction Score	16.0 Units on a scale Standard Error 0.27	15.8 Units on a scale Standard Error 0.28	15.9 Units on a scale Standard Error 0.29	14.2 Units on a scale Standard Error 0.28

SECONDARY outcome

Timeframe: Baseline through end of safety follow-up (Up To Week 44)

The hypoglycemia events were defined by participant reported events with blood glucose \< 54 mg/dL \[\<3.0 Millimole per Liter (mmol/L)\] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of post-baseline hypoglycemia was estimated by negative binomial model: Number of episodes = Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=230 Participants Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=228 Participants Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=229 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.	Insulin Glargine n=220 Participants Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Rate of Hypoglycemia With Blood Glucose < 54 mg/dL or Severe Hypoglycemia	0.0658 Episodes/participant/365.25 days Standard Error 0.02603	0.0890 Episodes/participant/365.25 days Standard Error 0.03196	0.0700 Episodes/participant/365.25 days Standard Error 0.02273	0.0538 Episodes/participant/365.25 days Standard Error 0.01594

Adverse Events

5 mg Tirzepatide

Serious events: 15 serious events

Other events: 174 other events

Deaths: 0 deaths

10 mg Tirzepatide

Serious events: 14 serious events

Other events: 201 other events

Deaths: 0 deaths

15 mg Tirzepatide

Serious events: 15 serious events

Other events: 193 other events

Deaths: 1 deaths

Insulin Glargine

Serious events: 20 serious events

Other events: 83 other events

Deaths: 2 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: LTE60

Serious adverse events
Measure	5 mg Tirzepatide n=230 participants at risk Participants received 5 mg tirzepatide administered SC QW.	10 mg Tirzepatide n=228 participants at risk Participants received 10 mg tirzepatide administered SC QW.	15 mg Tirzepatide n=229 participants at risk Participants received 15 mg tirzepatide administered SC QW.	Insulin Glargine n=220 participants at risk Participants received insulin glargine administered QD SC. The starting dose of insulin glargine was 6 IU/day at bedtime, titrated to a FBG between 72-100 mg/dL, following a TTT algorithm.
Blood and lymphatic system disorders Lymphoid tissue hyperplasia	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Atrial fibrillation	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Cardiac failure acute	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Coronary artery disease	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Myocardial infarction	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Ear and labyrinth disorders Vertigo	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.91% 2/220 • Number of events 2 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Eye disorders Cataract	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Eye disorders Macular oedema	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Anal fissure	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Colitis	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastritis	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Inguinal hernia	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Mechanical ileus	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Umbilical hernia	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Sudden cardiac death	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Sudden death	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Cholelithiasis	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Appendicitis	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Epididymitis	0.00% 0/134 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/126 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/129 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.85% 1/118 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Febrile infection	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Gastroenteritis	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Herpes zoster	0.43% 1/230 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pneumonia	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Urinary tract infection	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Femur fracture	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Meniscus injury	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Muscle rupture	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Road traffic accident	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Wrist fracture	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Cardiac function test	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Intervertebral disc protrusion	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Osteoarthritis	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/228 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Spinal osteoarthritis	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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 Spondylolisthesis	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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) Adenocarcinoma of colon	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/229 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.45% 1/220 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. 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) Benign breast neoplasm	0.00% 0/230 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/228 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.44% 1/229 • Number of events 1 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/220 • Baseline Through End of Safety Follow-Up (Up To Week 44). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.