A Study of LY4100511 (DC-853) Mass Balance and Absolute Bioavailability of LY4100511 in Healthy Male Participants

A Phase 1, Open-label, Two-part Study of the Absorption, Metabolism, Excretion, and Bioavailability of LY4100511 (DC-853) Following Administration of [14C]-LY4100511 in Healthy Male Participants

The study has two parts, Part A and Part B. The purpose of Part A is to determine the absorption, metabolism, and excretion (AME) of [14C]-LY4100511 and to characterize and determine the metabolites present in plasma, urine, and feces in healthy male participants after a single oral dose of LY4100511. The purpose of Part B is to determine the absolute bioavailability of LY4100511 in humans, to further analyze the rate and routes of excretion, including the mass balance, and to further investigate the pharmacokinetics (PK) of [14C]-LY4100511, LY4100511, and TRA.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LY4100511 (DC-853); Drug: [14C]-LY4100511 (DC-853) Administered oral dose; Drug: [14C]-LY4100511 (DC-853)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Fortrea Clinical Research Unit

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body mass index between 18.0 and 32.0 kilogram per square meter (kg/m2), inclusive, and a body weight of ≥50 kilogram (kg)
• In good health and determined by no clinically significant finding from medical history, 12-lead ECG and vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia, e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin is not acceptable) at screening and check-in, and from the physical examination at check-in, as assessed by the Investigator or designee
• History of a minimum of 1 bowel movement per day.
• Able to provide a fecal sample between check-in on Day-2 and oral dosing on Day 1.

Exclusion Criteria:

• Have a 12-lead ECG abnormality that, in the opinion of the Investigator

  • increases the risks associated with participating in the study
  • may confound ECG data analysis
  • a QTcF & > 450 msec
  • short PR interval & <120 msec or PR interval >220 msec
  • second- or third-degree atrioventricular block
  • intraventricular conduction delay with QRS 120 msec
  • right bundle branch block
  • left bundle branch block, or
  • Wolff Parkinson-White syndrome.
• Have a current or recent acute, active infection (for example, for at least 30 days before screening and up to check-in, participants must have no symptoms or signs of infection in the absence of any anti-infective treatment).
• Had any malignancy within the past 5 years. Exceptions: successfully treated basal cell skin carcinoma or squamous cell skin carcinoma, with no evidence of recurrence or metastatic disease within the 3 years prior to baseline.
• Are immunocompromised.
• Have inflammatory bowel disease (IBD)

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: Part A LY4100511 (tablet formulation) and [14C]-LY4100511 capsule; Participants will receive a single oral dose 1 or dose 2 unlabeled LY4100511 (tablet formulation) administered with a dose 1 [14C]-LY4100511 capsule containing approximately 100 µCi (3.7 MBq) of radioactivity in the fasted state	Drug: LY4100511 (DC-853); Administered oral dose; Drug: [14C]-LY4100511 (DC-853) Administered oral dose; Administered oral dose
Experimental: Part B LY4100511 (tablet formulation) and [14C]-LY4100511; Participants will receive a single oral dose 1 or dose 2 unlabeled LY4100511 (tablet formulation) in the fasted state, followed by a single intravenous (IV) dose of of [14C]-LY4100511, containing ≤1 μCi (≤37 kBq) of radioactivity, administered as an infusion.	Drug: LY4100511 (DC-853); Administered oral dose; Drug: [14C]-LY4100511 (DC-853); Administered IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Total Radioactivity Recovery and Excretion (TRA)	Total radioactivity recovery and excretion (fet1-t2 and Aet1-t2) in urine and feces (and vomitus, if available)	Up until Day 15
Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for [14C] LY4100511		Up until Day 15
Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for LY4100511		Up until Day 15
Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for TRA		Up until Day 15
Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for [14C] LY4100511		Up until Day 15
Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for LY4100511		Up until Day 15
Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for TRA		Up until Day 15
Part A: PK Maximum Observed Plasma Concentration (Cmax) for [14C] LY4100511		Up until Day 15
Part A: PK Maximum Observed Plasma Concentration (Cmax) for LY4100511		Up until Day 15
Part A: PK Maximum Observed Plasma Concentration (Cmax) for TRA		Up until Day 15
Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for [14C] LY4100511		Up until Day 15
Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for LY4100511		Up until Day 15
Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for TRA		Up until Day 15
Part A: PK Terminal Elimination Half Life (t1/2) for [14C] LY4100511		Up until Day 15
Part A: PK Terminal Elimination Half Life (t1/2) for LY4100511		Up until Day 15
Part A: PK Terminal Elimination Half Life (t1/2) for TRA		Up until Day 15
Part A: Urinary Recovery and Excretion of TRA (Aet1-t2)		Up until Day 15
Part A: Urinary Recovery and Excretion of [14C] LY4100511 (Aet1-t2)		Up until Day 15
Part A: Renal clearance of [14C] LY4100511 (CLR)		Up until Day 15
Part B: Pharmacokinetic (PK): absolute bioavailability (Fabs) of LY4100511		Up until Day 6
Part B: Recovery of TRA in urine and feces		Up until Day 6
Part B: Recovery of [14C]-LY4100511 in feces (Aet1-t2) following IV dosing		Up until Day 6
Part B: Recovery of [14C]-LY4100511 in urine (Aet1-t2) following IV dosing		Up until Day 6
Part B: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) of LY4100511 following IV dosing		Up until Day 6
Part B: PK Maximum Observed Plasma Concentration (Cmax) of LY4100511following IV dosing		Up until Day 6
Part B: PK Time to Maximum Observed Plasma Concentration (tmax) of LY4100511following IV dosing		Up until Day 6
Part B: PK Terminal Elimination Half Life (t1/2) following IV dosing		Up until Day 6
Part B: PK Clearance (CL) following IV dosing		Up until Day 6
Part B: PK renal clearance (CLr) following IV dosing [Time Frame: Up until Day 6]		Up until Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with One or More Adverse Events (AEs), and Serious Adverse Events (SAEs) considered by the investigator to be related to study drug administration	A summary of AEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events Module.	Up until Day 8

Collaborators and Investigators

• Sponsor: DICE Therapeutics, Inc., a wholly owned subsidiary of 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): August 23, 2024
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 23, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: DC-853; LY4100511
• Other Study ID Numbers: 27109; J5C-MC-FOAE (Other Identifier: DICE Therapeutics, a wholly owned subsidiary of 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