A Study of Absorption, Metabolism, Excretion, and Absolute Bioavailability of Carbon-14-Labelled [14C] Selpercatinib (LY3527723) in Healthy Male Participants
- Registration Number
- NCT05630287
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main purpose of this study is to compare the amount of selpercatinib that gets into the blood stream and how long it takes the body to get rid of it and also to assess the pharmacokinetics (PK), metabolism, and routes and extent of elimination of selpercatinib in healthy male participants. The study will last up to 59 days (Part 1) or 46 days (Part 2) including screening and 7-day safety follow-up.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 12
- Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²)
- Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study
- Participants will be surgically sterile for at least 90 days prior to Check in or, when sexually active with female partners of childbearing potential, will agree to use effective contraception methods or abstain from sexual intercourse from the time of first dose through 90 days after study drug administration
- Participation in any other radiolabeled investigational study drug trial within 12 months prior to Check-in
- Exposure to significant radiation (eg, serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to Check-in
- Use or intention to use any medications/products known strong inducers or inhibitors of Cytochrome P450 3A4 enzymes, including St. John's wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Carbon-14-labelled [14C]-Selpercatinib - Part 1 [14C]-Selpercatinib Participants received a single oral dose of 165 milligram (mg) of \[14C\]-Selpercatinib (containing approximately 40 µCi). Selpercatinib and [14C]-Selpercatinib - Part 2 Selpercatinib Participants received a single oral dose of 160 mg Selpercatinib followed by single dose of \<100 µg of \[14C\]-Selpercatinib (containing approximately 1 µCi) administered intravenously (IV). Selpercatinib and [14C]-Selpercatinib - Part 2 [14C]-Selpercatinib Participants received a single oral dose of 160 mg Selpercatinib followed by single dose of \<100 µg of \[14C\]-Selpercatinib (containing approximately 1 µCi) administered intravenously (IV).
- Primary Outcome Measures
Name Time Method PK: AUClast of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity PK: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUClast of \[14C\] Selpercatinib in plasma and whole blood
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: t½ of Selpercatinib in plasma
PK: t½ of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: t½ of \[14C\] Selpercatinib in plasma and whole blood
PK: Apparent Systemic Clearance (CL/F) of Selpercatinibin Plasma (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: CL/F of Selpercatinib in plasma
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Selpercatinib in Plasma (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Vz/F of Selpercatinib in plasma
PK: Plasma Selpercatinib/Total Radioactivity AUC0-24 Ratio (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose PK: AUC0-24 of Selpercatinib in plasma/AUC0-24 of total radioactivity in plasma
PK: Blood/Plasma Total Radioactivity AUC0-24 Ratio (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose PK: AUC0-24 of total radioactivity in whole blood/AUC0-24 of total radioactivity in whole blood
PK: AUClast of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUClast of Selpercatinib in plasma
PK: AUClast of [14C] Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUClast of \[14C\] Selpercatinib in plasma
PK: AUC0-inf of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUC0-inf of Selpercatinib in plasma
PK: AUC0-inf of [14C] Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUC0-inf of \[14C\] Selpercatinib in plasma
PK: Cmax of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Cmax of Selpercatinib in plasma
PK: Cmax of [14C] Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Cmax of \[14C\] Selpercatinib in plasma
PK: Tmax of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Tmax of Selpercatinib in plasma
PK: Tmax of [14C] Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Tmax of \[14C\] Selpercatinib in plasma
PK: t½ of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: t½ of Selpercatinib in plasma
PK: t½ of [14C] Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: t½ of \[14C\] Selpercatinib in plasma
PK: CL/F of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: CL/F of Selpercatinib in plasma
PK: Systemic Clearance (CL) of [14C] Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: CL of \[14C\] Selpercatinib in plasma
PK: Vz/F of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Vz/F of Selpercatinib in plasma
PK: Volume of Distribution During the Terminal Phase (Vz) of [14C] Selpercatinib in Plasma (Part 2) Pre-dose up to 168 hour post-dose PK: Vz of \[14C\] Selpercatinib in plasma
PK: Volume of Distribution at Steady State (Vss) of [14C] Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Vss of \[14C\] Selpercatinib in plasma
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Selpercatinib in Plasma (Part 1) PK: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUClast of Selpercatinib in plasma
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma (Part 1) PK: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUC0-inf of Selpercatinib in plasma
PK: AUC0-inf of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: AUC0-inf of \[14C\] Selpercatinib in plasma and whole blood
PK: Area Under the Concentration-time Curve, From Time 0 to Hour 24 (AUC0-24) of Selpercatinib in Plasma (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose PK: AUC0-24 of Selpercatinib in plasma
PK: (AUC0-24) of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose PK: AUC0-24 of \[14C\] Selpercatinib in plasma and whole blood
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Cmax of Selpercatinib in plasma
PK: Cmax of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Cmax of \[14C\] Selpercatinib in plasma and whole blood
PK: Time to Reach Cmax (Tmax) of Selpercatinib in Plasma (Part 1) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Tmax of Selpercatinib in plasma
PK: Tmax of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose PK: Tmax of \[14C\] Selpercatinib in plasma and whole blood
PK: Absolute Bioavailability (F) of Selpercatinib in Plasma (Part 2) Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose Absolute bioavailability was determined by comparing the plasma exposure of LOXO-292 following oral dosing with the plasma exposure of \[14C\]-LOXO-292 following IV dosing.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
LabCorp CRU, Inc.
🇺🇸Madison, Wisconsin, United States