Clinical trial NCT06627088: A Study of LY4100511 (DC-853) Mass Balance and Absolute Bioavailability of LY4100511 in Healthy Male Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: LY4100511
DC-853
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-10-04
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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.
* 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)

Primary outcomes:
measure: Part A: Total Radioactivity Recovery and Excretion (TRA)
timeFrame: Up until Day 15
measure: Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for [14C] LY4100511
timeFrame: Up until Day 15
measure: Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for LY4100511
timeFrame: Up until Day 15
measure: Part A: Pharmacokinetic (PK): Area Under the Concentration from Time 0 to Infinity (AUC0-∞) for TRA
timeFrame: Up until Day 15
measure: Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for [14C] LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) for TRA
timeFrame: Up until Day 15
measure: Part A: PK Maximum Observed Plasma Concentration (Cmax) for [14C] LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Maximum Observed Plasma Concentration (Cmax) for LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Maximum Observed Plasma Concentration (Cmax) for TRA
timeFrame: Up until Day 15
measure: Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for [14C] LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Time to Maximum Observed Plasma Concentration (tmax) for TRA
timeFrame: Up until Day 15
measure: Part A: PK Terminal Elimination Half Life (t1/2) for [14C] LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Terminal Elimination Half Life (t1/2) for LY4100511
timeFrame: Up until Day 15
measure: Part A: PK Terminal Elimination Half Life (t1/2) for TRA
timeFrame: Up until Day 15
measure: Part A: Urinary Recovery and Excretion of TRA (Aet1-t2)
timeFrame: Up until Day 15
measure: Part A: Urinary Recovery and Excretion of [14C] LY4100511 (Aet1-t2)
timeFrame: Up until Day 15
measure: Part A: Renal clearance of [14C] LY4100511 (CLR)
timeFrame: Up until Day 15
measure: Part B: Pharmacokinetic (PK): absolute bioavailability (Fabs) of LY4100511
timeFrame: Up until Day 6
measure: Part B: Recovery of TRA in urine and feces
timeFrame: Up until Day 6
measure: Part B: Recovery of [14C]-LY4100511 in feces (Aet1-t2) following IV dosing
timeFrame: Up until Day 6
measure: Part B: Recovery of [14C]-LY4100511 in urine (Aet1-t2) following IV dosing
timeFrame: Up until Day 6
measure: Part B: PK Area Under Concentration from 0 to Last Measurable Concentration (AUC0-tlast) of LY4100511 following IV dosing
timeFrame: Up until Day 6
measure: Part B: PK Maximum Observed Plasma Concentration (Cmax) of LY4100511following IV dosing
timeFrame: Up until Day 6
measure: Part B: PK Time to Maximum Observed Plasma Concentration (tmax) of LY4100511following IV dosing
timeFrame: Up until Day 6
measure: Part B: PK Terminal Elimination Half Life (t1/2) following IV dosing
timeFrame: Up until Day 6
measure: Part B: PK Clearance (CL) following IV dosing
timeFrame: Up until Day 6
measure: Part B: PK renal clearance (CLr) following IV dosing [Time Frame: Up until Day 6]
timeFrame: Up until Day 6
Secondary outcomes:
measure: 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
timeFrame: Up until Day 8
Other outcomes:
Locations:
city: Madison
country: United States
facility: Fortrea Clinical Research Unit
state: Wisconsin
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: