A Study of Tirzepatide (LY3298176) in Participants With Obesity Disease

Study Overview
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Brief Summary
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The main purpose of this study is to learn more about tirzepatide in participants with obesity disease. The study will also measure how Tirzepatide affects body weight with a low-calorie diet and increased physical activity. The study will last around 72 Weeks.

Official Title
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Efficacy and Safety of Once-Weekly Tirzepatide in Participants With Obesity Disease: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-J)

Conditions
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Obesity

Intervention / Treatment
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* Drug: Tirzepatide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a BMI of greater than or equal to ≥27 kg/m² and <less than 35 kg/m² with at least 2 obesity-related health problems or ≥35 kg/m² with at least 1 obesity-related health problems. Health problems are IGT, hyperlipidemia, or NAFLD. Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight. Exclusion Criteria: Have diabetes. Acute or chronic liver disease other than NAFLD. Have a self-reported change in body weight >5 kg within 3 months prior to screening. Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months. Have renal impairment measured as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, calculated by Japanese Society of Nephrology coefficient-modified Chronic Kidney Disease-Epidemiology equation during screening. Have a known clinically significant gastric emptying abnormality. Have had a history of chronic or acute pancreatitis. Have thyroid-stimulating hormone outside of the range of 0.4 to 6.0 micro units per milliliter (μIU/mL) at screening. Have obesity induced by other endocrinologic disorders or diagnosed monogenetic or syndromic forms of obesity. Have a history of significant active or unstable major depressive disorder or other severe psychiatric disorder within the last 2 years. Have a cardiovascular condition within 3 months prior to randomization Have a family or personal history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome type 2.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide Regimen A<br>Tirzepatide Regimen A administered subcutaneously (SC) | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: Tirzepatide Regimen B<br>Tirzepatide Regimen B administered subcutaneously (SC) | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Placebo administered SC | Other: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve ≥5% Body Weight Reduction | Percentage of Participants Who Achieve ≥5% Body Weight Reduction | Week 72 | 
| Percent Change in Body Weight | Percent Change in Body Weight | Baseline, 72 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Had Improvement in Obesity-related Health Problems | Percentage of participants who had improvement in at least 2 obesity-related health problems in participants with a baseline body mass index (BMI) ≥27 and <35 kilogram per square meter (kg/m²) or improvement in at least 1 obesity-related health problems in participants with a baseline BMI ≥35 kg/m² | Week 72 | 
| Change from Baseline in Oral Glucose Tolerance (OGTT) 2-hr Glucose (Only for Participant with Impaired Glucose Tolerance [IGT] at Baseline) | Change from Baseline in OGTT 2-hr Glucose (Only for Participants with IGT at Baseline) | Baseline, Week 72 | 
| Change from Baseline in Fasting Glucose (Only for Participants with IGT at Baseline) | Change from Baseline in Fasting Glucose (Only for Participants with IGT at Baseline) | Baseline, Week 72 | 
| Change from Baseline in Fasting Lipids [Triglycerides (TG)] (Only for Participants with hyperlipidemia at Baseline) | Change from Baseline in Fasting Lipids TG (Only for Participants with hyperlipidemia at Baseline) | Baseline, Week 72 | 
| Change from Baseline in Hepatic Fat Fraction (HFF) (only for participants diagnosed as Non-alcoholic Fatty Liver Disease [NAFLD] by Magnetic Resonance Imaging (MRI) at Baseline) | Change from Baseline in HFF (only for participants diagnosed as NAFLD by MRI at Baseline) | Baseline, Week 72 | 
| Percentage of Participants Who Achieved Improvements of IGT (Only for Participants with IGT at Baseline) | Percentage of Participants Who Achieved Improvements of IGT (Only for Participants with IGT at Baseline) | Week 72 | 
| Percentage of Participants Who Achieved Improvements of Hyperlipidemia (Only for Participants with Hyperlipidemia at Baseline) | Percentage of Participants Who Achieved Improvements of Hyperlipidemia (only for participants with hyperlipidemia at Baseline) | Week 72 | 
| Percentage of Participants Who Achieved Improvements of NAFLD (only for participants who are diagnosed as NAFLD by Magnetic Resonance Imaging (MRI) at Baseline) | Percentage of Participants Who Achieved Improvements of NAFLD (only for participants who are diagnosed as NAFLD by MRI at Baseline) | Week 72 | 
| 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 | 
| Change from Baseline in Absolute Body Weight | Change from Baseline in Absolute Body Weight | Baseline, Week 72 | 
| Change from Baseline in BMI | Change from Baseline in BMI | Baseline, Week 72 | 
| Change from Baseline in Visceral Adipose Tissue (VAT) | Change from Baseline in VAT will be collected by single slice imaging at the umbilicus level in a supine position using computerized tomography (CT). | Baseline, Week 72 | 
| Change from Baseline in Subcutaneous Adipose Tissue (SAT) | Change from Baseline in SAT will be collected by single slice imaging at the umbilicus level in a supine position using CT. | Baseline, Week 72 | 
| Change from Baseline in VAT/SAT Ratio | Change from Baseline in VAT/SAT Ratio | Baseline, Week 72 | 
| Percentage of Participants Who Achieve VAT <100 square centimeter (cm²) from Baseline (only for participants with VAT≥100 cm2 at Baseline) | Percentage of Participants Who Achieve VAT <100 cm² from Baseline (only for participants with VAT≥100 cm2 at Baseline) | Week 72 | 
| Change from Baseline in Waist Circumference | Change from Baseline in Waist Circumference | Baseline, Week 72 | 
| Change from Baseline in Hemoglobin A1c (HbA1c) | Change from Baseline in HbA1c | Baseline, Week 72 | 
| Change from Baseline in Fasting Insulin | Change from Baseline in Fasting Insulin | Baseline, Week 72 | 
| Change from Baseline in Systolic Blood Pressure | Change from Baseline in Systolic Blood Pressure | Baseline, Week 72 | 
| Change from Baseline in Diastolic Blood Pressure | Change from Baseline in Diastolic Blood Pressure | Baseline, Week 72 | 
| Change from Baseline in Short Form 36 Version 2 Health Survey (SF-36v2) Acute Form Physical Functioning Domain Score | Change from Baseline in SF-36v2 Acute Form Physical Functioning Domain Score | Baseline, Week 72 | 
| Change from Baseline in Change in Impact of Weight on Quality-of-Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score | Change from Baseline in Change in IWQOL-Lite-CT Physical Function score | Baseline, Week 72 | 
| Change from Baseline in Euro Quality of Life Five Dimensions (EQ-5D-5L) | Change from Baseline in Euro Quality of Life Five Dimensions (EQ-5D-5L) | Baseline, Week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolism and Nutrition Disorder, Obesity Related Health Problems, Obesity Disease