A Study of LY3549492 in Healthy Participants and Participants With Overweight or Obesity

A Phase-1, Parallel-Design, Open-Label, Randomized, Multiple-Dose Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of LY3549492 in Healthy Participants With Overweight or Obesity

The purpose of this study is to see how safe and well-tolerated the drug LY3549492 is and how it behaves in the body, when given in multiple doses to healthy people who are overweight or have obesity. Participation in the study will last approximately 8 weeks.

Study Overview

• Status: Completed
• Conditions: Healthy; Obesity; Overweight
• Intervention / Treatment: Drug: LY3549492

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• 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: Yes

Description

Inclusion Criteria:

• Have a hemoglobin A1c level of less than 6.5 percent (%) at screening.
• Have a body mass index (BMI) of 25.0 to 45.0 kilogram per square meter (kg/m²), inclusive, at screening
• Participants assigned male at birth (AMAB) or participants assigned female at birth (AFAB) who are individual of childbearing potential (INOCBP) Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

• Have obesity induced by endocrine disorders such as Cushing's syndrome or Prader Willi syndrome.

• Have any of the following conditions at screening,

  • supine systolic blood pressure of 160 millimeter of mercury (mmHg) or greater
  • supine diastolic blood pressure of 100 mmHg or greater, or
  • resting pulse rate of greater than 95 beats per minute (bpm) or less than 45 bpm. (Note: white-coat hypertension is excluded; therefore, if a repeated measurement of blood pressure after at least 5 minutes shows values within the range, the participant can be included).

• Have had any of the following within 6-months prior to screening

  • myocardial infarction
  • unstable angina
  • coronary artery bypass graft
  • percutaneous coronary intervention. (Note: diagnostic angiograms are permitted)
  • transient ischemic attack
  • cerebrovascular accident or decompensated congestive heart failure, or
  • New York Health Association Class III or IV heart failure.
• Have serum triglyceride of 5 millimoles per liter (mmol/L) or greater (442 milligrams per deciliter [mg/dL]) at screening
• Have had any exposure to glucagon-like peptide-1 (GLP-1) analogs or other related compounds within the 3 months prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3549492 (Treatment Group 1); LY3549492 administered orally.	Drug: LY3549492; Administered orally
Experimental: LY3549492 (Treatment Group 2); LY3549492 administered orally.	Drug: LY3549492; Administered orally
Experimental: LY3549492 (Treatment Group 3); LY3549492 administered orally.	Drug: LY3549492; Administered orally
Experimental: LY3549492 (Treatment Group 4); LY3549492 administered orally.	Drug: LY3549492; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of SAEs regardless of causality, will be reported in the Reported Adverse Events module	Baseline through end of the Follow-up Period (Week 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3549492	PK: Cmax of LY3549492	Predose on Day 1 through end of the Follow-up Period (Week 10)
PK: Observed Drug Trough Concentration (Ctrough) of LY3549492	PK: Ctrough of LY3549492	Predose on Day 1 through end of the Follow-up Period (Week 10)
PK: Area Under the Concentration Versus Time Curve (AUC) of LY3549492	PK: AUC of LY3549492	Predose on Day 1 through end of the Follow-up Period (Week 10)

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 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Actual): July 16, 2026
• Study Completion (Actual): July 16, 2026

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: August 21, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: 27786; J3H-MC-GZNJ (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