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

DICE Therapeutics

Status and phase: Completed; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06627088

27109

J5C-MC-FOAE (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: LY4100511 (DC-853)

Drug: LY4100511 (DC-853)

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

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

Experimental group

Description:

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.

Treatment:

Drug: LY4100511 (DC-853)

Drug: LY4100511 (DC-853)

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