A Study of Once-Daily Oral Orforglipron (LY3502970) in Japanese Adult Participants With Obesity Disease

Study Overview
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Brief Summary
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The main purpose of this study is to investigate the efficacy and safety of oral orforglipron in participants with obesity disease with obesity-related health problems.

Official Title
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A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral LY3502970 Compared With Placebo in Japanese Adult Participants With Obesity Disease

Conditions
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Obesity

Intervention / Treatment
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* Drug: Orforglipron
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with a BMI ≥27 kg/m² and <35 kg/m² and at least 2 obesity-related health problems (treated or untreated), OR a BMI ≥35 kg/m² and at least 1 obesity-related health problem (treated or untreated). At least one obesity-related health problem should be hypertension, dyslipidemia or T2D (approximately 25% of participants). Have a history of at least one self-reported unsuccessful dietary effort to lose body weight. Males and females may participate in this trial. Female participants must not be pregnant, intending to be pregnant, breastfeeding, or intending to breastfeed. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. No male contraception is required except in compliance with specific local government study requirements. Exclusion Criteria: For participants with Type 2 Diabetes (T2D): Have Type 1 Diabetes (T1D), history of ketoacidosis or hyperosmolar state/coma, or any other types of diabetes except T2D. Have had 1 or more episode of severe hypoglycemia and/or 1 or more episode of hypoglycemia unawareness within the 180 days prior to screening. Have renal impairment measured as estimated glomerular filtration rate (eGFR) <15 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. For participants without Type 2 diabetes (T2D): Have any type of diabetes with hemoglobin A1c (HbA1c) ≥6.5 %. Have a self-reported change in body weight >5 kg (11 pounds) within 90 days prior to screening. Have chronic kidney disease. Have lupus or rheumatoid arthritis. Have the following cardiovascular conditions within 90 days prior to screening. Have acute or chronic hepatitis.

Ages Eligible for Study
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Minimum Age: 18 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: Orforglipron Dose 1<br>Participants will receive orforglipron orally. | Drug: Orforglipron<br>* Administered orally<br>|
| Experimental: Orforglipron Dose 2<br>Participants will receive orforglipron orally. | Drug: Orforglipron<br>* Administered orally<br>|
| Experimental: Orforglipron Dose 3<br>Participants will receive orforglipron orally. | Drug: Orforglipron<br>* Administered orally<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction |  | Baseline to Week 72 | 
| Percentage of Participants Who Achieve ≥15% Body Weight Reduction |  | Baseline to Week 72 | 
| Percentage of Participants Who Achieve ≥20% Body Weight Reduction |  | Baseline to Week 72 | 
| Mean Change from Baseline in Body Mass Index (BMI) |  | Baseline, Week 72 | 
| Percentage of Participants Who Had Improvements in Hypertension |  | Baseline to Week 72 | 
| Percentage of Participants Who Had Improvements in Dyslipidemia (only for participants with Dyslipidemia at baseline) |  | Baseline to Week 72 | 
| Percentage of Participants Who Achieve HbA1c Target value (<6.5% (48 mmol/mol) at Week 72 (only T2D at Baseline): |  | Baseline to Week 72 | 
| Mean Change from Baseline in Visceral Adipose Tissue (VAT) |  | Baseline, Week 72 | 
| Mean Change from Baseline in Waist Circumference at Umbilical Level |  | Baseline, Week 72 | 
| Mean Change from Baseline in Systolic Blood Pressure (SBP) |  | Baseline, Week 72 | 
| Mean Change from Baseline in non-High Density Lipoprotein (HDL) |  | Baseline, Week 72 | 
| Mean Change from Baseline in HDL |  | Baseline, Week 72 | 
| Mean Change from Baseline in Triglycerides |  | Baseline, Week 72 | 
| Mean Change from Baseline in Fasting Glucose |  | Baseline, Week 72 | 
| Mean Change from Baseline in Hemoglobin A1c (HbA1c) |  | Baseline, Week 72 | 
| Mean Change from Baseline in High-sensitivity C-reactive Protein |  | Baseline, Week 72 | 
| Mean Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Scores |  | Baseline, Week 72 | 
| Mean Change from Baseline in IMPACT of Weight on Quality-of-Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function, Physical, and Psychosocial Composite Score |  | Baseline, Week 72 | 
| Time to Onset of Type 2 Diabetes (T2D) (only non T2D at Baseline) |  | Baseline to Week 72 | 
| Pharmacokinetics (PK): Plasma Concentration of Orforglipron |  | Baseline to Week 72 | 

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