Trial Outcomes & Findings for A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss (NCT NCT04660643)
NCT ID: NCT04660643
Last Updated: 2024-05-22
Results Overview
Least square (LS) mean was analysed by mixed model repeated measures (MMRM) model with randomization + analysis country + sex + interactive web response system (IWRS) MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
783 participants
Primary outcome timeframe
Randomization (Week 36), Week 88
Results posted on
2024-05-22
Participant Flow
* Open-label lead-in period: Baseline (week 0) to week 36: Participants received weekly doses of tirzepatide SC escalated every 4 weeks until they attained a maximum tolerated dose (MTD). * Double-blind study period (randomized period including the safety follow-up): Randomization (week 36) to week 92: At week 36, those who completed the lead-in treatment were randomized 1:1 to tirzepatide MTD and placebo, treated up to week 88, and followed up for safety after 4 weeks off treatment, at week 92.
Participant milestones
| Measure |
Tirzepatide (lead-in)
Participants received weekly doses of tirzepatide subcutaneously (SC) for 36 weeks, starting at 2.5 milligrams (mg) and increasing by 2.5 mg every 4 weeks, as tolerated, up to the maximum tolerated dose (MTD) of either 10 mg or 15 mg.
|
Placebo
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|---|
|
Open-label Lead-in Period (Week 0 - 36)
STARTED
|
783
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Received at Least 1 Dose of Study Drug
|
782
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Completed 36-weeks of Treatment (i.e., Reaching and Tolerating the MTD at Week 36)
|
670
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
COMPLETED
|
671
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
NOT COMPLETED
|
112
|
0
|
0
|
|
Double-blind Study Period (Week 36 - 92)
STARTED
|
0
|
335
|
335
|
|
Double-blind Study Period (Week 36 - 92)
Received at Least 1 Dose of Study Drug
|
0
|
335
|
335
|
|
Double-blind Study Period (Week 36 - 92)
COMPLETED
|
0
|
290
|
310
|
|
Double-blind Study Period (Week 36 - 92)
NOT COMPLETED
|
0
|
45
|
25
|
Reasons for withdrawal
| Measure |
Tirzepatide (lead-in)
Participants received weekly doses of tirzepatide subcutaneously (SC) for 36 weeks, starting at 2.5 milligrams (mg) and increasing by 2.5 mg every 4 weeks, as tolerated, up to the maximum tolerated dose (MTD) of either 10 mg or 15 mg.
|
Placebo
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|---|
|
Open-label Lead-in Period (Week 0 - 36)
Adverse Event
|
50
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Death
|
1
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Lost to Follow-up
|
14
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Pregnancy
|
1
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Physician Decision
|
1
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Protocol deviation
|
10
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Withdrawal by Subject
|
32
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Covid-19
|
1
|
0
|
0
|
|
Open-label Lead-in Period (Week 0 - 36)
Other - as reported by the investigator
|
2
|
0
|
0
|
|
Double-blind Study Period (Week 36 - 92)
Death
|
0
|
1
|
1
|
|
Double-blind Study Period (Week 36 - 92)
Lost to Follow-up
|
0
|
10
|
8
|
|
Double-blind Study Period (Week 36 - 92)
Pregnancy
|
0
|
2
|
1
|
|
Double-blind Study Period (Week 36 - 92)
Withdrawal by Subject
|
0
|
22
|
13
|
|
Double-blind Study Period (Week 36 - 92)
Protocol deviation
|
0
|
1
|
2
|
|
Double-blind Study Period (Week 36 - 92)
Other - as reported by the investigator
|
0
|
8
|
0
|
|
Double-blind Study Period (Week 36 - 92)
Perceived excessive weight loss
|
0
|
1
|
0
|
Baseline Characteristics
A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss
Baseline characteristics by cohort
| Measure |
Placebo
n=335 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=335 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
Total
n=670 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47.15 years
STANDARD_DEVIATION 12.38 • n=99 Participants
|
48.27 years
STANDARD_DEVIATION 12.79 • n=107 Participants
|
47.71 years
STANDARD_DEVIATION 12.59 • n=206 Participants
|
|
Sex: Female, Male
Female
|
237 Participants
n=99 Participants
|
236 Participants
n=107 Participants
|
473 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
98 Participants
n=99 Participants
|
99 Participants
n=107 Participants
|
197 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
155 Participants
n=99 Participants
|
141 Participants
n=107 Participants
|
296 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
180 Participants
n=99 Participants
|
193 Participants
n=107 Participants
|
373 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
22 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
36 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
273 Participants
n=99 Participants
|
264 Participants
n=107 Participants
|
537 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
Argentina
|
56 Participants
n=99 Participants
|
55 Participants
n=107 Participants
|
111 Participants
n=206 Participants
|
|
Region of Enrollment
Brazil
|
46 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
89 Participants
n=206 Participants
|
|
Region of Enrollment
Taiwan
|
17 Participants
n=99 Participants
|
21 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
216 Participants
n=99 Participants
|
216 Participants
n=107 Participants
|
432 Participants
n=206 Participants
|
|
Body weight
|
107.79 kilogram (kg)
STANDARD_DEVIATION 23.66 • n=99 Participants
|
106.82 kilogram (kg)
STANDARD_DEVIATION 20.94 • n=107 Participants
|
107.3 kilogram (kg)
STANDARD_DEVIATION 22.33 • n=206 Participants
|
PRIMARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
Least square (LS) mean was analysed by mixed model repeated measures (MMRM) model with randomization + analysis country + sex + interactive web response system (IWRS) MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percent Change From Randomization in Body Weight at Week 88
|
14.8 percent change
Standard Error 0.53
|
-6.7 percent change
Standard Error 0.52
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 64Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percent Change From Randomization in Body Weight at Week 64
|
9.9 percent change
Standard Error 0.38
|
-6.0 percent change
Standard Error 0.37
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Body Weight
|
11.9 kilogram (kg)
Standard Error 0.43
|
-5.7 kilogram (kg)
Standard Error 0.42
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Waist Circumference
|
8.3 centimetre (cm)
Standard Error 0.44
|
-4.6 centimetre (cm)
Standard Error 0.43
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Body Mass Index (BMI)
|
4.3 kilogram per square metre (kg/m^2)
Standard Error 0.16
|
-2.1 kilogram per square metre (kg/m^2)
Standard Error 0.15
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=310 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=325 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Fasting Glucose
|
7.74 milligrams per deciliter (mg/dL)
Standard Error 0.548
|
-0.90 milligrams per deciliter (mg/dL)
Standard Error 0.528
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=311 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=325 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Hemoglobin A1c (HbA1c)
|
0.25 percentage of HbA1c
Standard Error 0.017
|
-0.08 percentage of HbA1c
Standard Error 0.017
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=311 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=324 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percent Change From Randomization in Fasting Insulin
|
23.3 percent change
Standard Error 4.37
|
-15.4 percent change
Standard Error 2.88
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for the respective lipid parameters, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=273 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=298 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
Total Cholesterol
|
8.30 percent change
Standard Error 0.943
|
2.29 percent change
Standard Error 0.852
|
|
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
LDL Cholesterol
|
3.43 percent change
Standard Error 1.368
|
-3.36 percent change
Standard Error 1.218
|
|
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
HDL Cholesterol
|
14.6 percent change
Standard Error 1.06
|
18.3 percent change
Standard Error 1.05
|
|
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
VLDL Cholesterol
|
14.7 percent change
Standard Error 2.32
|
-7.8 percent change
Standard Error 1.77
|
|
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
Triglycerides
|
15.6 percent change
Standard Error 2.39
|
-8.2 percent change
Standard Error 1.81
|
|
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
FFA
|
-2.9 percent change
Standard Error 2.98
|
-13.4 percent change
Standard Error 2.54
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
LS mean change was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP
|
3.2 millimetre of mercury (mmHg)
Standard Error 0.44
|
-0.4 millimetre of mercury (mmHg)
Standard Error 0.42
|
|
Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP
|
8.4 millimetre of mercury (mmHg)
Standard Error 0.64
|
2.1 millimetre of mercury (mmHg)
Standard Error 0.61
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
The SF-36v2 acute form assesses health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10-items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores. LS mean was analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=270 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=295 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain Score
|
-1.8 T-score
Standard Error 0.32
|
0.8 T-score
Standard Error 0.31
|
SECONDARY outcome
Timeframe: Randomization (Week 36), Week 88Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
The IWQOL Lite-CT consists of 20 items, assessing 2 primary domains of obesity related HRQoL: Physical (7 items) and Psychosocial (13 items). A 5-item subset of the Physical domain - the Physical Function composite - is also supported. Items in the Physical Function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better health-related quality of life. LS mean was analysed by ANCOVA model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=272 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=293 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Randomization in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Function Composite Score
|
-5.0 score on a scale
Standard Error 0.95
|
4.4 score on a scale
Standard Error 0.91
|
SECONDARY outcome
Timeframe: Week 88Population: All randomized participants who received at least one dose of the study drug, had weight loss in the open label lead-in period and at least one post-randomization value for this outcome, excluding data after discontinuation of the study drug.
Percentage of Participants Who Maintain at least 80% of the Body Weight Lost During the Open-Label Lead-In Period was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment\*Time as variables.
Outcome measures
| Measure |
Placebo
n=326 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period
|
13.50 percentage of participants
|
93.37 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (Week 0) to Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction from baseline was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment\*Time as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline
≥5% body weight reduction from baseline
|
69.00 percentage of participants
|
98.49 percentage of participants
|
|
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline
≥10% body weight reduction from baseline
|
44.38 percentage of participants
|
93.98 percentage of participants
|
|
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline
≥15% body weight reduction from baseline
|
24.01 percentage of participants
|
87.05 percentage of participants
|
|
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline
≥20% body weight reduction from baseline
|
11.55 percentage of participants
|
72.59 percentage of participants
|
SECONDARY outcome
Timeframe: Randomization (Week 36) to Week 88Population: All randomized participants who received at least one dose of the study drug, lost \>=5% of their weight in the open label period, excluding data after discontinuation of study drug.
Time to first occurrence of participants returning to \>95% baseline weight for those who lost ≥5% during the open-label lead-in period.
Outcome measures
| Measure |
Placebo
n=327 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% During the Open-Label Lead-In Period
|
NA weeks
There were not enough events to estimate the median and confidence interval.
|
NA weeks
There were not enough events to estimate the median and confidence interval.
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + BMI at randomization (kg/m\^2) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in BMI
|
-3.6 kg/m^2
Standard Error 0.16
|
-10.0 kg/m^2
Standard Error 0.15
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in Body Weight
|
-10.0 kg
Standard Error 0.43
|
-27.6 kg
Standard Error 0.42
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percent Change From Baseline in Body Weight
|
-9.5 percent change
Standard Error 0.40
|
-26.0 percent change
Standard Error 0.39
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in Waist Circumference
|
-9.1 cm
Standard Error 0.53
|
-22.8 cm
Standard Error 0.52
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=310 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=325 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in Fasting Glucose
|
-1.72 mg/dL
Standard Error 0.543
|
-10.63 mg/dL
Standard Error 0.522
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=311 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=325 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in HbA1c
|
-0.22 percentage of HbA1c
Standard Error 0.018
|
-0.57 percentage of HbA1c
Standard Error 0.017
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=300 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=314 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percent Change From Baseline in Fasting Insulin
|
-29.8 percent change
Standard Error 2.52
|
-54.1 percent change
Standard Error 1.57
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for the respective lipid parameters, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=273 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=298 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
Total Cholesterol
|
2.16 percent change
Standard Error 0.919
|
-5.01 percent change
Standard Error 0.817
|
|
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
LDL Cholesterol
|
2.62 percent change
Standard Error 1.371
|
-5.21 percent change
Standard Error 1.207
|
|
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
HDL Cholesterol
|
9.44 percent change
Standard Error 1.093
|
12.29 percent change
Standard Error 1.071
|
|
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
VLDL Cholesterol
|
-15.6 percent change
Standard Error 1.82
|
-32.6 percent change
Standard Error 1.37
|
|
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
Triglycerides
|
-15.3 percent change
Standard Error 1.84
|
-33.3 percent change
Standard Error 1.38
|
|
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
FFA
|
-9.69 percent change
Standard Error 2.811
|
-20.38 percent change
Standard Error 2.360
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=329 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=332 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in SBP, DBP
SBP
|
-2.4 mmHg
Standard Error 0.66
|
-9.3 mmHg
Standard Error 0.63
|
|
Change From Baseline in SBP, DBP
DBP
|
-1.7 mmHg
Standard Error 0.46
|
-5.5 mmHg
Standard Error 0.44
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
The SF-36v2 acute form assesses health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10-items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores. LS mean was analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=271 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=296 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in SF 36v2 Acute Form - Physical Functioning Domain Score
|
3.7 T-score
Standard Error 0.36
|
6.3 T-score
Standard Error 0.34
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 88Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
The IWQOL Lite-CT consists of 20 items, assessing 2 primary domains of obesity related HRQoL: Physical (7 items) and Psychosocial (13 items). A 5-item subset of the Physical domain - the Physical Function composite - is also supported. Items in the Physical Function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better health-related quality of life. LS mean was analysed by ANCOVA model with baseline + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Outcome measures
| Measure |
Placebo
n=273 Participants
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=294 Participants
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|
|
Change From Baseline in IWQOL-Lite-CT - Physical Function Composite Score
|
16.7 score on a scale
Standard Error 1.01
|
26.0 score on a scale
Standard Error 0.97
|
Adverse Events
Tirzepatide (lead-in)
Serious events: 16 serious events
Other events: 559 other events
Deaths: 1 deaths
Placebo
Serious events: 10 serious events
Other events: 100 other events
Deaths: 1 deaths
Tirzepatide MTD
Serious events: 10 serious events
Other events: 124 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Tirzepatide (lead-in)
n=782 participants at risk
Participants received weekly doses of tirzepatide SC for 36 weeks, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks, as tolerated, up to the MTD of either 10 mg or 15 mg.
|
Placebo
n=335 participants at risk
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=335 participants at risk
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Cardiac disorders
Atrial fibrillation
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Cardiac disorders
Atrioventricular block
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Endocrine disorders
Goitre
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Eye disorders
Visual impairment
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 2 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 2 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Peptic ulcer
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 2 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.51%
4/782 • Number of events 4 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.90%
3/335 • Number of events 3 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.26%
2/782 • Number of events 2 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.60%
2/335 • Number of events 2 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Covid-19
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Covid-19 pneumonia
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Hepatitis viral
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Peritonitis
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Investigations
Lipase increased
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.26%
2/782 • Number of events 2 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-hodgkin's lymphoma
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour perforation
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Nervous system disorders
Cerebral infarction
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Psychiatric disorders
Mental status changes
|
0.13%
1/782 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Surgical and medical procedures
Aortic aneurysm repair
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Vascular disorders
Haematoma
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Vascular disorders
Hypotension
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Vascular disorders
Shock haemorrhagic
|
0.00%
0/782 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.00%
0/335 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
Other adverse events
| Measure |
Tirzepatide (lead-in)
n=782 participants at risk
Participants received weekly doses of tirzepatide SC for 36 weeks, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks, as tolerated, up to the MTD of either 10 mg or 15 mg.
|
Placebo
n=335 participants at risk
Participants received weekly doses of placebo SC for 52 weeks.
|
Tirzepatide MTD
n=335 participants at risk
Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
6.1%
48/782 • Number of events 71 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
1.8%
6/335 • Number of events 9 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
3.3%
11/335 • Number of events 12 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Constipation
|
20.7%
162/782 • Number of events 202 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
2.4%
8/335 • Number of events 9 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
3.6%
12/335 • Number of events 17 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Diarrhoea
|
21.1%
165/782 • Number of events 329 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
4.8%
16/335 • Number of events 21 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
10.7%
36/335 • Number of events 112 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Dyspepsia
|
8.1%
63/782 • Number of events 78 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
8.8%
69/782 • Number of events 90 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.30%
1/335 • Number of events 1 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
1.2%
4/335 • Number of events 4 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Nausea
|
35.5%
278/782 • Number of events 600 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
2.7%
9/335 • Number of events 11 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
8.1%
27/335 • Number of events 75 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Gastrointestinal disorders
Vomiting
|
16.4%
128/782 • Number of events 275 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
1.2%
4/335 • Number of events 7 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
5.4%
18/335 • Number of events 36 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
General disorders
Fatigue
|
6.8%
53/782 • Number of events 61 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.60%
2/335 • Number of events 2 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
2.7%
9/335 • Number of events 12 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
General disorders
Injection site reaction
|
8.2%
64/782 • Number of events 424 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
0.60%
2/335 • Number of events 4 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
2.1%
7/335 • Number of events 107 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Covid-19
|
10.5%
82/782 • Number of events 83 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
14.9%
50/335 • Number of events 51 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
14.0%
47/335 • Number of events 47 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
3.3%
26/782 • Number of events 28 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
5.4%
18/335 • Number of events 18 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
2.4%
8/335 • Number of events 9 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.5%
74/782 • Number of events 145 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
1.2%
4/335 • Number of events 7 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
2.1%
7/335 • Number of events 14 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Nervous system disorders
Headache
|
7.2%
56/782 • Number of events 72 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
3.0%
10/335 • Number of events 10 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
1.5%
5/335 • Number of events 6 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.1%
40/782 • Number of events 40 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
1.5%
5/335 • Number of events 5 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
3.9%
13/335 • Number of events 13 • Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.
All participants who received at least one dose of the study drug. Based on the planned safety analysis, adverse events were collected per the treatment regimen, irrespective of dose.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60