A Study of LY3532226 in Participants With Obesity

A Dose-Escalation Phase 1, Investigator- and Participant-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of LY3532226 in Participants With Obesity

The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY3532226 in participants with obesity. Blood tests will be performed to check how much LY3532226 gets into the bloodstream and how long it takes the body to eliminate it following weekly or monthly administration. Part A of the study will last approximately 16 weeks, excluding screening period. Part B of the study will last approximately 20 weeks, excluding the screening period. Part C of the study will last approximately 8 weeks, excluding the screening period.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: LY3532226

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 138623
    • Lilly Centre for Clinical Pharmacology
• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Fortrea Clinical Research Unit
  • Texas
    • Dallas, Texas, United States, 75247
      • Fortrea Clinical Research Unit
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Fortrea Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a body weight not exceeding 150 kilograms (kg) or 330 pounds (lb) and body mass index (BMI) within the range of 30 to 40 kilogram per square meter (kg/m²)
• Have had a stable body weight that is less than or equal to 5% change in body weight for 3 months prior to screening and enrollment

Exclusion Criteria:

• Have a lifetime history of a suicide attempt
• Have a history or presence of psychiatric disorders, including a history of major depressive disorder within the last 2 years
• Have a baseline Patient Health Questionnaire-9 (PHQ-9) score of 15 or greater, and/or a score of 2 or greater for either of the first 2 questions on the PHQ-9 questionnaire
• Have a known clinically significant gastric emptying abnormality, have undergone gastric bypass surgery or restrictive bariatric surgery
• Have taken approved or investigational medication for weight loss, within the previous 3 months or 5 half-lives of study screening, whichever is earlier
• Intend to use any weight-loss medications during study participation
• Have obesity induced by other endocrinologic disorders or diagnosed monogenetic or syndromic forms of obesity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Part A); Placebo administered SC	Drug: Placebo; Administered SC
Placebo Comparator: Placebo (Part B); Placebo administered SC	Drug: Placebo; Administered SC
Experimental: LY3532226 (Part A); LY3532226 administered subcutaneously (SC)	Drug: LY3532226; Administered SC
Experimental: LY3532226 (Part B); LY3532226 administered SC	Drug: LY3532226; Administered SC
Experimental: LY3532226 (Part C); LY3532226 administered SC	Drug: LY3532226; Administered SC
Placebo Comparator: Placebo (Part C); Placebo administered SC	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of TEAEs and SAEs, regardless of causality, will be reported in the Reported Adverse Events module	Baseline to Study Completion (Up to 16 Weeks)
Part B: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of TEAEs and SAEs, regardless of causality, will be reported in the Reported Adverse Events module	Baseline to Study Completion (Up to 20 Weeks)
Part C: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of TEAEs and SAEs, regardless of causality, will be reported in the Reported Adverse Events module	Baseline to Study Completion (Up to 8 Weeks)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3532226	PK: Cmax of LY3532226	Predose on Day 1 through Week 16
Part A: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3532226	PK: AUC of LY3532226	Predose on Day 1 through Week 16
Part B: PK: Cmax of LY3532226	PK: Cmax of LY3532226	Predose on Day 1 through Week 20
Part B: PK: AUC of LY3532226	PK: AUC of LY3532226	Predose on Day 1 through Week 20
Part C: Pharmacodynamic (PD): Change in insulin sensitivity index (Si)	Part C: PD: Change in Si	Baseline up to Approximately Week 4

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• Lilly Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2024
• Primary Completion (Actual): December 12, 2025
• Study Completion (Actual): December 12, 2025

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 18835; J2V-MC-GZLD (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No