A Study of Carbon-14-Labeled [14C]-LY3549492 in Healthy Participants

An Open-label, Two-part Study of the Disposition and Absolute Bioavailability of [14C]-LY3549492 in Healthy Participants

The main purpose of this study is to measure how much of the study drug gets into the bloodstream and how long it takes the body to get rid of it. This study will be conducted in healthy males and has two parts. In Part A, participants will receive carbon-14 (14C) radiolabeled LY3549492 ([14C] LY3549492) given by mouth. In Part B, participants will receive LY3549492 by mouth. Three hours later, participants will receive [14C] LY3549492 given into a vein.

The radioactive substance C14 will be incorporated into the study drug to investigate the study drug and breakdown products to find out how much of these passes from blood into urine, stool, and breath.

The study will last about 2 months in Part A and about 1½ months in Part B. This includes screening, treatment, and follow-up visits.

Study Overview

• Status: Completed
• Conditions: Healthy Male
• Intervention / Treatment: Drug: LY3549492; Drug: [14C]-LY3549492; Drug: [14C]-LY3549492

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds
    • Holbeck, Leeds, United Kingdom, LS11 9EH
      • Fortrea Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG).
• Participants who have safety laboratory test results within normal reference ranges, or results with acceptable deviations that are deemed not clinically significant by the investigator.
• Body mass index (BMI) within the range of 20.0 to 40.0 kilograms per meter squared (kg/m2), inclusive.
• Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

• Have known allergies to LY3549492, glucagon-like peptide-1 (GLP-1) non-peptide agonist (NPA)-related compounds or any components of the formulation as appropriate, or history of atopy.
• Have a clinical diagnosis of a long QT syndrome.
• Have any abnormality in the 12-lead ECG at screening that, in the opinion of the investigator, may increase the risk associated with participation in the study or may confound ECG data analysis.
• Have significant history of any current serious medical condition.
• Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis) or have an elevation in serum amylase or lipase (>1.0×Upper Limit Normal (ULN)).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carbon-14-Labeled [14C]-LY3549492 - Part A; Carbon-14-Labeled [14C]-LY3549492 administered as oral solution.	Drug: [14C]-LY3549492; Administered as oral solution.; Drug: [14C]-LY3549492; Administered as IV infusion.
Experimental: LY3549492 + [14C]-LY3549492 - Part B; LY3549492 administered as oral solution followed 3 hours later by [14C] LY3549492 will be administered as intravenous (IV) infusion.	Drug: LY3549492; Administered orally.; Drug: [14C]-LY3549492; Administered as oral solution.; Drug: [14C]-LY3549492; Administered as IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Excretion of Total Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose in Part A	Urinary Excretion of Total Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose	Predose up to Day 24 postdose in Part A
Fecal Excretion of Total Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose in Part A	Fecal Excretion of Total Radioactivity Over Time Expressed as a Percentage of the Total	Predose up to Day 24 postdose in Part A
Pharmacokinetic (PK): Area Under the Curve (AUC) for Oral Determination of Absolute Bioavailability (F) of LY3549492 in Part B	PK: AUC for oral determination of absolute bioavailability (F) of LY3549492	Predose up to Day 7 postdose in Part B
PK: AUC for Intravenous (IV) Determination of Absolute Bioavailability (F) of LY3549492 in Part B	PK: AUC for IV determination of absolute bioavailability (F) of LY3549492	Predose up to Day 7 postdose in Part B

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Area Under the Concentration (AUC) for Radioactivity in Plasma and Whole Blood in Part A	PK: AUC for radioactivity	Predose up to Day 24 postdose in Part A
PK: Maximum Concentration (Cmax) for Radioactivity in Plasma and Whole Blood in Part A	PK: Cmax for radioactivity	Predose up to Day 24 postdose in Part A
PK: AUC of LY3549492 in Plasma in Part A	PK: AUC of LY3549492 in plasma	Predose up to Day 24 postdose in Part A
PK: Cmax of LY3549492 in Plasma in Part A	PK: Cmax of LY3549492 in plasma	Predose up to Day 24 postdose in Part A
Total Radioactivity Recovered in Urine, Feces, and Expired Air (if applicable) in Part A	Total radioactivity recovered in urine, feces, and expired air (if applicable) in Part A	Predose up to Day 24 postdose in Part A
Total Number of Metabolites and Identification of Metabolites of LY3549492 in Part A	Total number of metabolites and identification of metabolites of LY3549492	Predose up to Day 24 postdose in Part A
PK: AUC of LY3549492, [14C]-LY3549492, and Total Radioactivity in Plasma in Part B	AUC of LY3549492, [14C]-LY3549492, and total radioactivity in plasma in Part B	Predose up to Day 7 postdose in Part B
PK: Cmax of LY3549492, [14C]-LY3549492, and Total Radioactivity in Plasma in Part B	Cmax of LY3549492, [14C]-LY3549492, and total radioactivity in plasma in Part B	Predose up to Day 7 postdose in Part B
Total Radioactivity Recovered in Urine and Feces in Part B	Total radioactivity recovered in urine and feces in Part B	Predose up to Day 7 postdose in Part B

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

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Actual): February 15, 2024
• Study Completion (Actual): February 15, 2024

Study Registration Dates

• First Submitted: December 20, 2023
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Actual): January 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 18348; J3H-MC-GZNC (Other Identifier: Eli Lilly and Company); U1111-1293-8652 (Other Identifier: UTN)

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: No
• Studies a U.S. FDA-regulated device product: No