A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight

Study Overview
=================
Brief Summary
-----------------
This is a study of tirzepatide in participants with overweight and obesity. The main purpose is to learn more about how tirzepatide affects body weight. The study has two phases: A main phase and an extension phase. The main phase of the study will last 72 weeks. Participants with prediabetes will continue in the extension for another 2 years.

Official Title
-----------------
Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight- Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

Conditions
-----------------
Overweight, Obesity

Intervention / Treatment
-----------------
* Drug: Tirzepatide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass Index (BMI) ≥30 kilograms per square meter (kg/m²), or ≥27 kg/m² and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease History of at least one unsuccessful dietary effort to lose body weight Exclusion Criteria: Diabetes mellitus Change in body weight greater than 5 kg within 3 months prior to starting study Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity History of pancreatitis Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years Any lifetime history of a suicide attempt

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg Tirzepatide<br>5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: 10 mg Tirzepatide<br>10 mg tirzepatide administered SC once a week. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: 15 mg Tirzepatide<br>15 mg tirzepatide administered SC once a week. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Placebo administered SC once a week. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Body Weight | Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 72 | 
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction | Percentage of participants who achieve ≥5% body weight reduction. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 20 | 
| Percent Change From Baseline in Body Weight | Percent Change from Baseline in Body Weight. | Baseline, Week 176 | 
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction | Percentage of Participants who Achieve ≥10% Body Weight Reduction | Week 72 | 
| Percentage of Participants Who Achieve ≥15% Body Weight Reduction | Percentage of participants who achieve ≥15% body weight reduction. | Week 72 | 
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction | Percentage of Participants who Achieve ≥5% Body Weight Reduction. | Week 176 | 
| Percentage of Participants Who Achieve ≥20% Body Weight Reduction | Percentage of participants who achieve ≥20% body weight reduction. | Week 72 | 
| Change From Baseline in Waist Circumference | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 72 | 
| Change From Baseline in Body Mass Index (BMI) | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 72 | 
| Change From Baseline in Fasting Glucose | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 72 | 
| Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | Fasting Insulin is a test used to measure the amount of insulin in the body. Results are reported as model-based estimates and SE from MMRM analysis using log transformation. | Baseline, Week 72 | 
| Time to Onset of Type 2 Diabetes | Time to Onset of Type 2 Diabetes | Baseline through Week 176 | 
| Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 72 | 
| Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation. | Baseline, Week 72 | 
| Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. | Baseline, Week 72 | 
| Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. | Baseline, Week 72 | 
| Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. | Baseline, Week 72 | 
| Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. | Baseline, Week 72 | 
| Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. | Baseline, Week 72 | 
| Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 72 | 
| Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment*time (Type III sum of squares) in the model. | Baseline, Week 72 | 
| Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) | The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 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 while the remaining domains assess functioning in the past week. Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. | Baseline, Week 72 | 
| Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 | The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (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 quality of life. | Baseline, Week 72 | 
| Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | PK: Steady State AUC of Tirzepatide. each participant will be assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose. | Week 8, 16, and 36, at 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metabolism and Nutrition Disorder, Prediabetes