A Study of Absorption, Metabolism, Excretion, and Absolute Bioavailability of Carbon-14-Labelled [14C] Selpercatinib (LY3527723) in Healthy Male Participants

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1, Open-label, Two-part Study to Investigate the Absorption, Metabolism, and Excretion, and the Absolute Bioavailability of [14C]-LOXO-292 in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: [14C] Selpercatinib
* Drug: Selpercatinib
* Drug: [14C] Selpercatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [14C] Selpercatinib - Part 1<br>[14C] Selpercatinib administered as an oral solution | Drug: [14C] Selpercatinib<br>* Administered as an oral solution<br>* Other names: LOXO-292;|
| Experimental: Selpercatinib and [14C] Selpercatinib - Part 2<br>Single oral dose of Selpercatinib followed 2 hours later by single dose of [14C] Selpercatinib administered as an intravenous (IV) push. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;Drug: [14C] Selpercatinib<br>* Administered intravenously<br>* Other names: LOXO-292;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: AUClast of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: AUClast of [14C] Selpercatinib in plasma and whole blood (Part 1) for Total Radioactivity | PK: AUClast of [14C] Selpercatinib in plasma and whole blood | Pre-dose up to 168 hour post-dose | 
| PK: Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) of Selpercatinib in plasma (Part 1) | PK: AUC0-inf of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: AUC0-inf of [14C] Selpercatinib in plasma and whole blood (Part 1) for Total Radioactivity | PK: AUC0-inf of [14C] Selpercatinib in plasma and whole blood | Pre-dose up to 168 hour post-dose | 
| PK: Area under the concentration-time curve, from time 0 to Hour 24 (AUC0-24) of Selpercatinib in plasma (Part 1) | PK: AUC0-24 of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: (AUC0-24) of [14C] Selpercatinib in plasma and whole blood (Part 1) for Total Radioactivity | PK: AUC0-24 of [14C] Selpercatinib in plasma and whole blood | Pre-dose up to 168 hour post-dose | 
| PK: Maximum observed concentration (Cmax) of Selpercatinib in plasma (Part 1) | PK: Cmax of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Cmax of [14C] Selpercatinib in plasma and whole blood (Part 1) for Total Radioactivity | PK: Cmax of [14C] Selpercatinib in plasma and whole blood | Pre-dose up to 168 hour post-dose | 
| PK: Time to reach Cmax (Tmax) of Selpercatinib in plasma (Part 1) | PK: Tmax of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Tmax of [14C] Selpercatinib in plasma and whole blood (Part 1) for Total Radioactivity | PK: Tmax of [14C] Selpercatinib in plasma and whole blood | Pre-dose up to 168 hour post-dose | 
| PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib in plasma (Part 1) | PK: t½ of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: t½ of [14C] Selpercatinib in plasma and whole blood (Part 1) for Total Radioactivity | PK: t½ of [14C] Selpercatinib in plasma and whole blood | Pre-dose up to 168 hour post-dose | 
| PK: Apparent systemic clearance (CL/F) of Selpercatinibin plasma (Part 1) | PK: CL/F of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Apparent volume of distribution during the terminal phase (Vz/F) of Selpercatinib in plasma (Part 1) | PK: Vz/F of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Plasma Selpercatinib/Total Radioactivity AUC0-24 Ratio (Part 1) | PK: AUC0-24 of Selpercatinib in plasma/AUC0-24 of total radioactivity in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Blood/Plasma Total Radioactivity AUC0-24 Ratio (Part 1) | PK: AUC0-24 of total radioactivity in whole blood/AUC0-24 of total radioactivity in plasma | Pre-dose up to 168 hour post-dose | 
| PK: AUClast of Selpercatinib in plasma (Part 2) | PK: AUClast of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: AUClast of [14C] Selpercatinib in plasma (Part 2) | PK: AUClast of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: AUC0-inf of Selpercatinib in plasma (Part 2) | PK: AUC0-inf of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: AUC0-inf of [14C] Selpercatinib in plasma (Part 2) | PK: AUC0-inf of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Cmax of Selpercatinib in plasma (Part 2) | PK: Cmax of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Cmax of [14C] Selpercatinib in plasma (Part 2) | PK: Cmax of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Tmax of Selpercatinib in plasma (Part 2) | PK: Tmax of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Tmax of [14C] Selpercatinib in plasma (Part 2) | PK: Tmax of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: t½ of Selpercatinib in plasma (Part 2) | PK: t½ of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: t½ of [14C] Selpercatinib in plasma (Part 2) | PK: t½ of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: CL/F of Selpercatinib in plasma (Part 2) | PK: CL/F of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Systemic clearance (CL) of [14C] Selpercatinib in plasma (Part 2) | PK: CL of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Vz/F of Selpercatinib in plasma (Part 2) | PK: Vz/F of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Volume of distribution during the terminal phase (Vz) of [14C] Selpercatinib in plasma (Part 2) | PK: Vz of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Volume of distribution at steady state (Vss) of [14C] Selpercatinib in plasma (Part 2) | PK: Vss of [14C] Selpercatinib in plasma | Pre-dose up to 168 hour post-dose | 
| PK: Absolute bioavailability (F) of Selpercatinib in plasma (Part 2) | PK: F of Selpercatinib in plasma | Pre-dose up to 168 hour post-dose |