Healthy
Conditions
Keywords
LY4100511, DC-853
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.
Interventions
Administered oral dose
DRUG[14C]-LY4100511 (DC-853) Administered oral dose
Administered oral dose
DRUG[14C]-LY4100511 (DC-853)
Administered IV infusion
Sponsors
DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: PK renal clearance (CLr) following IV dosing [Time Frame: Up until Day 6] | Up until Day 6 | — |
| Part A: Urinary Recovery and Excretion of TRA (Aet1-t2) | 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: Total Radioactivity Recovery and Excretion (TRA) | 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 | 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: 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | A summary of AEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events Module. |
Countries
United States
Outcome results
None listed