A Study of LY3463251 in Healthy Participants

NCT03764774 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 17110J1D-MC-GZAA
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability (side effects) of single (Part A) and multiple (Part B) doses of the study drug when it is administered subcutaneously (under the skin) into the abdomen. This is a two-part study. Participants will enroll in only one part. For each participant, Part A will last about 10 weeks and Part B will last about 23 weeks, including screening.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With One or More Adverse Event(s) (AEs), All Causalities

  A summary of serious adverse events (SAEs) and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

  Baseline through follow up in Part A (up to Day 42); Baseline through follow up in Part B (up to Day 123)

Secondary Outcomes (6)

• Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3463251 Part A

  Day 1: Predose, 6, 12, 24, 48, 72, 96, 120, 168, 264, 360, 528, 696, and 1008 hr postdose

• PK: Maximum Observed Concentration of LY3463251 Part B

  Day 1: Predose, 6, 12, 24, 48, 72, and 120 hours (hr) postdose; Day 8: Predose; Day 15: Predose; Day 28: Predose; Day 57: Predose; Day 78: Predose, and Day 79: 24 hr postdose

• PK: Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tlast]) of LY3463251 Part A

  Day 1: Predose, 6, 12, 24, 48, 72, 96, 120, 168, 264, 360, 528, 696, and 1008 hr postdose

• PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUC[0-tau)] for LY3463251 Part B

  Day 1: Predose, 6, 12, 24, 48, 72, 120, and 168 hours (hr) postdose: Day 78: Predose, 24, 48, 168, 336, 696, 1080 hr postdose

• Pharmacodynamics (PD): AUC (0-2hours) of Glucose Part B

  PD: Day -2; Predose: Day 30 and Day 85 (Part B)

Study Arms (14)

0.01 Milligram (mg) LY3463251 Part A Cohort 1

EXPERIMENTAL

Single dose of 0.01 mg LY3463251 administered subcutaneously (SC) on Day 1.

Drug: LY3463251

0.03 mg LY3463251 Part A Cohort 2

EXPERIMENTAL

Single dose of 0.03 mg LY3463251 administered SC on Day 1.

Drug: LY3463251

0.1 mg LY3463251 Part A Cohort 3

EXPERIMENTAL

Single dose of 0.1 mg LY3463251 administered SC on Day 1.

Drug: LY3463251

0.3 mg LY3463251 Part A Cohort 4

EXPERIMENTAL

Single dose of 0.3 mg LY3463251 administered SC on Day 1.

Drug: LY3463251

1 mg LY3463251 Part A Cohort 5

EXPERIMENTAL

Single dose of 1 mg LY3463251 administered SC on Day 1.

Drug: LY3463251

3 mg LY3463251 Part A Cohort 6

EXPERIMENTAL

Single dose of 3 mg LY3463251 administered SC on Day 1.

Drug: LY3463251

10 mg LY3463251 Part A Cohort 7

EXPERIMENTAL

Single dose of 10 mg LY3463251 administered SC on Day 1.

Drug: LY3463251

24 mg LY3463251 Part A Cohort 8

EXPERIMENTAL

Single dose of 24 mg LY3463251 administered SC on Day 1.

Drug: LY3463251

Placebo Single Dose

PLACEBO COMPARATOR

Single dose of placebo administered SC.

Drug: Placebo

1 mg LY3463251 Part B Cohort 1

EXPERIMENTAL

1 mg LY3463251 administered SC, once weekly (QW) for 12 weeks on Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

Drug: LY3463251

3 mg LY3465231 Part B Cohort 2

EXPERIMENTAL

3 mg LY3463251 administered SC, QW for 12 weeks on Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

Drug: LY3463251

3/6/9 mg LY3463251 Part B Cohort 3

EXPERIMENTAL

3 mg LY3463251 administered SC, QW on Days 1 and 8. 6 mg LY3463251 administered SC, QW on Days 15 and 22. 9 mg LY3463251 administered SC, QW on Days 29. 36, 43, 50, 57, 64, 71, and 78.

Drug: LY3463251

3/9/15/24 mg LY3463251 Part B Cohort

EXPERIMENTAL

3 mg LY3463251 administered SC, QW on Days 1 and 8. 9 mg LY3463251 administered SC, QW on Days 15 and 22. 15 mg LY3463251 administered SC, QW on Days 29 and 36. 24 mg LY3463251 administered SC, QW on Days 43, 50, 57, 64, 71, and 78.

Drug: LY3463251

Placebo Multiple Dose

PLACEBO COMPARATOR

Placebo administered SC, QW for 12 weeks.

Drug: Placebo

Interventions

LY3463251 DRUG

Administered SC

0.01 Milligram (mg) LY3463251 Part A Cohort 1; 0.03 mg LY3463251 Part A Cohort 2; 0.1 mg LY3463251 Part A Cohort 3; 0.3 mg LY3463251 Part A Cohort 4; 1 mg LY3463251 Part A Cohort 5; 1 mg LY3463251 Part B Cohort 1; 10 mg LY3463251 Part A Cohort 7; 24 mg LY3463251 Part A Cohort 8; 3 mg LY3463251 Part A Cohort 6; 3 mg LY3465231 Part B Cohort 2; 3/6/9 mg LY3463251 Part B Cohort 3; 3/9/15/24 mg LY3463251 Part B Cohort

Placebo DRUG

Administered SC

Placebo Multiple Dose; Placebo Single Dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males and females

You may not qualify if:

• Diagnosed with Type 1 or Type 2 diabetes
• Women who are of childbearing potential or who are breastfeeding
• Donated blood of more than 500 millilitres (mL) within the previous 3 months of study screening
• Have used any tobacco product within 3 months of Day -1, or are unwilling to refrain from the use of tobacco during the study

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Covance Clinical Research Inc

Daytona Beach, Florida, 32117, United States

Location

Related Publications (1)

• Benichou O, Coskun T, Gonciarz MD, Garhyan P, Adams AC, Du Y, Dunbar JD, Martin JA, Mather KJ, Pickard RT, Reynolds VL, Robins DA, Zvada SP, Emmerson PJ. Discovery, development, and clinical proof of mechanism of LY3463251, a long-acting GDF15 receptor agonist. Cell Metab. 2023 Feb 7;35(2):274-286.e10. doi: 10.1016/j.cmet.2022.12.011. Epub 2023 Jan 10.

  PMID: 36630958 DERIVED

Limitations and Caveats

Cohort 4 was terminated early because data from previous cohorts suggested a low probability of achieving competitive weight loss at tolerable doses.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2018
• First Posted: December 5, 2018
• Study Start: December 6, 2018
• Primary Completion: December 7, 2020
• Study Completion: December 7, 2020
• Last Updated: November 4, 2025
• Results First Posted: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)