NCT06627088

Completed

Phase 1

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

DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company1 site in 1 country24 target enrollmentAugust 23, 2024

ConditionsHealthy

InterventionsLY4100511 (DC-853)[14C]-LY4100511 (DC-853) Administered oral dose [14C]-LY4100511 (DC-853)

DrugsLY4100511 (DC-853)[14C]-LY4100511 (DC-853) Administered oral dose [14C]-LY4100511 (DC-853)

Overview

Phase: Phase 1
Intervention: LY4100511 (DC-853)
Conditions: Healthy
Sponsor: DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company
Enrollment: 24
Locations: 1
Primary Endpoint: Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for TRA
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 23, 2024

End Date

December 31, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

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

Responsible Party

Sponsor

Eligibility Criteria

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.

Arms & Interventions

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

Intervention: LY4100511 (DC-853)

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

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

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.

Intervention: LY4100511 (DC-853)

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

Intervention: [14C]-LY4100511 (DC-853)

Outcomes

Primary Outcomes

Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for TRA

Time Frame: Up until Day 15

Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for [14C] LY4100511

Time Frame: Up until Day 15

Part A: Total Radioactivity Recovery and Excretion (TRA)

Time Frame: Up until Day 15

Total radioactivity recovery and excretion (fet1-t2 and Aet1-t2) in urine and feces (and vomitus, if available)

Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for [14C] LY4100511

Time Frame: Up until Day 15

Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for LY4100511

Time Frame: Up until Day 15

Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for LY4100511

Time Frame: Up until Day 15

Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for TRA

Time Frame: Up until Day 15

Part A: PK Maximum Observed Plasma Concentration (Cmax) for [14C] LY4100511

Time Frame: Up until Day 15

Part A: PK Maximum Observed Plasma Concentration (Cmax) for LY4100511

Time Frame: Up until Day 15

Part A: PK Maximum Observed Plasma Concentration (Cmax) for TRA

Time Frame: Up until Day 15

Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for [14C] LY4100511

Time Frame: Up until Day 15

Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for LY4100511

Time Frame: Up until Day 15

Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for TRA

Time Frame: Up until Day 15

Part B: Recovery of TRA in urine and feces

Time Frame: Up until Day 6

Part A: PK Terminal Elimination Half Life (t1/2) for [14C] LY4100511

Time Frame: Up until Day 15

Part A: PK Terminal Elimination Half Life (t1/2) for LY4100511

Time Frame: Up until Day 15

Part A: PK Terminal Elimination Half Life (t1/2) for TRA

Time Frame: Up until Day 15

Part A: Urinary Recovery and Excretion of TRA (Aet1-t2)

Time Frame: Up until Day 15

Part A: Urinary Recovery and Excretion of [14C] LY4100511 (Aet1-t2)

Time Frame: Up until Day 15

Part A: Renal clearance of [14C] LY4100511 (CLR)

Time Frame: Up until Day 15

Part B: Pharmacokinetic (PK): absolute bioavailability (Fabs) of LY4100511

Time Frame: Up until Day 6

Part B: Recovery of [14C]-LY4100511 in feces (Aet1-t2) following IV dosing

Time Frame: Up until Day 6

Part B: Recovery of [14C]-LY4100511 in urine (Aet1-t2) following IV dosing

Time Frame: Up until Day 6

Part B: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) of LY4100511 following IV dosing

Time Frame: Up until Day 6

Part B: PK Maximum Observed Plasma Concentration (Cmax) of LY4100511following IV dosing

Time Frame: Up until Day 6

Part B: PK Time to Maximum Observed Plasma Concentration (tmax) of LY4100511following IV dosing

Time Frame: Up until Day 6

Part B: PK Terminal Elimination Half Life (t1/2) following IV dosing

Time Frame: Up until Day 6

Part B: PK Clearance (CL) following IV dosing

Time Frame: Up until Day 6

Part B: PK renal clearance (CLr) following IV dosing [Time Frame: Up until Day 6]

Time Frame: Up until Day 6

Secondary Outcomes

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)