A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight

Study Overview
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Brief Summary
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The main purpose of this study, performed under a master protocol, is to investigate weight management efficacy and safety with LY3305677 compared with placebo and in adult participants with obesity or overweight. The study will last about 62 weeks.

Official Title
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A Phase 2, Parallel-Group, Double-Blind, 4-Arm Study to Investigate Weight Management With LY3305677 Compared With Placebo and in Adult Participants With Obesity or Overweight

Conditions
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Obesity, Overweight and Obesity

Intervention / Treatment
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* Drug: LY3305677
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: W8M-MC-OXA1: Are males and females who agree to abide by the reproductive and contraceptive requirements W8M-MC-CWMM: Have a BMI ≥27 kilograms per square meter (kg/m²) with at least one of the following weight-related comorbidities: hypertension: on blood pressure (BP)-lowering medication. dyslipidemia: on lipid-lowering medication cardiovascular (CV) disease: for example, ischemic CV disease, New York Heart Association (NYHA) Functional Classification Class 1 or II Heart Failure obstructive sleep apnea Have had a stable body weight for the 3 months prior to randomization (<5% body weight gain and/or loss). Exclusion Criteria: W8M-MC-OXA1: Have any prior diagnosis of diabetes mellitus, that is type 2 diabetes mellitus (T2DM), or rare forms of diabetes mellitus, except gestational diabetes. Have any of the following cardiovascular conditions within 6 months prior to screening: acute myocardial infarction cerebrovascular accident (stroke) unstable angina, or hospitalization due to congestive heart failure (CHF). Have a history of acute or chronic pancreatitis. Have a history of New York Heart Association (NYHA) Functional Classification I IV CHF. Participants with hypertension who do not have well-controlled blood pressure (BP) (>140/90 mmHg), regardless of antihypertensive treatment. Participants receiving treatment for hypertension should be on a stable antihypertensive regimen for at least 3 months prior to screening. Note: If the investigator anticipates a need to add antihypertensive medication during the study, the participant should not be included in the ambulatory blood pressure monitoring (ABPM) procedures. W8M-MC-CWMM: Have a prior or planned surgical treatment for obesity, except prior liposuction or abdominoplasty, if performed >1 year prior to screening. Have type 1 diabetes mellitus, latent autoimmune diabetes in adults, or history of ketoacidosis or hyperosmolar coma. Have poorly controlled hypertension. Have signs and symptoms of any liver disease other than nonalcoholic fatty liver disease. Have any of the following cardiovascular conditions within 3 months prior to Screening: acute myocardial infarction cerebrovascular accident (stroke) unstable angina, or hospitalization due to congestive heart failure. Have a history of symptomatic gallbladder disease within the past 2 years. Have a lifetime history of suicide attempts.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: LY3305677 Dose 1<br>Participants will receive LY3305677 subcutaneously (SC). | Drug: LY3305677<br>* Administered SC<br>|
| Experimental: LY3305677 Dose 2<br>Participants will receive LY3305677 SC. | Drug: LY3305677<br>* Administered SC<br>|
| Experimental: LY3305677 Dose 3<br>Participants will receive LY3305677 SC. | Drug: LY3305677<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Participants will receive LY3305677 matching placebo. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Body Weight |  | Baseline, Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Body Weight |  | Baseline, Week 48 | 
| Change from Baseline in Body Weight |  | Baseline, Week 32 | 
| Change from Baseline in Body Weight |  | Baseline, Week 48 | 
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction |  | Baseline to Week 32 | 
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction |  | Baseline to Week 48 | 
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction |  | Baseline to Week 32 | 
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction |  | Baseline to Week 48 | 
| Change from Baseline in Body Mass Index (BMI) |  | Baseline, Week 48 | 
| Change from Baseline in BMI |  | Baseline, Week 32 | 
| Absolute Change from Baseline in Liver Fat Content by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) |  | Baseline, Week 32 | 
| Percent Change from Baseline in Liver Fat Content by MRI-PDFF |  | Baseline, Week 32 | 
| Absolute Change from Baseline in Liver Fat Content by MRI-PDFF |  | Baseline, Week 48 | 
| Percent Change from Baseline in Liver Fat Content by MRI-PDFF |  | Baseline, Week 48 | 
| Pharmacokinetics (PK): Area Under the Curve (AUC) of LY3305677 |  | Baseline to Week 48 | 
| PK: Maximum Concentration (Cmax) of LY3305677 |  | Baseline to Week 48 | 
| Number of Participants with Treatment Emergent Drug Antibodies (TE-ADAs) |  | Baseline to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Incretins, Weight Loss, Overnutrition