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

NCT06627088 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 27109J5C-MC-FOAE
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

LY4100511; DC-853

Outcome Measures

Primary Outcomes (29)

• 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 Outcomes (1)

• 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

  Up until Day 8

Study Arms (2)

Part A LY4100511 (tablet formulation) and [14C]-LY4100511 capsule

EXPERIMENTAL

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); Drug: [14C]-LY4100511 (DC-853) Administered oral dose

Part B LY4100511 (tablet formulation) and [14C]-LY4100511

EXPERIMENTAL

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); Drug: [14C]-LY4100511 (DC-853)

Interventions

LY4100511 (DC-853) DRUG

Administered oral dose

Part A LY4100511 (tablet formulation) and [14C]-LY4100511 capsule

[14C]-LY4100511 (DC-853) Administered oral dose DRUG

Administered oral dose

Part A LY4100511 (tablet formulation) and [14C]-LY4100511 capsule

[14C]-LY4100511 (DC-853) DRUG

Administered IV infusion

Part B LY4100511 (tablet formulation) and [14C]-LY4100511

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: individuals assigned male at birth
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company: lead

Study Sites (1)

Fortrea Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2024
• First Posted: October 4, 2024
• Study Start: August 23, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)