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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Selpercatinib; Drug: [14C]-Selpercatinib; Drug: [14C]-Selpercatinib

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • LabCorp CRU, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carbon-14-labelled [14C]-Selpercatinib - Part 1; Participants received a single oral dose of 165 milligram (mg) of [14C]-Selpercatinib (containing approximately 40 µCi).	Drug: [14C]-Selpercatinib; Administered as an oral solution; Other Names: LOXO-292; LY3527723; Drug: [14C]-Selpercatinib; Administered intravenously; Other Names: LOXO-292; LY3527723
Experimental: Selpercatinib and [14C]-Selpercatinib - Part 2; 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).	Drug: Selpercatinib; Administered orally; Other Names: LOXO-292; LY3527723; Drug: [14C]-Selpercatinib; Administered as an oral solution; Other Names: LOXO-292; LY3527723; Drug: [14C]-Selpercatinib; Administered intravenously; Other Names: LOXO-292; LY3527723

What is the study measuring?

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	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 (Part 1) for Total Radioactivity	PK: AUClast of [14C] Selpercatinib in plasma and whole blood	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: 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	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 [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity	PK: AUC0-inf of [14C] Selpercatinib in plasma and whole blood	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
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	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 (Part 1) for Total Radioactivity	PK: AUC0-24 of [14C] Selpercatinib in plasma and whole blood	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma (Part 1)	PK: Cmax of Selpercatinib in plasma	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 (Part 1) for Total Radioactivity	PK: Cmax of [14C] Selpercatinib in plasma and whole blood	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Time to Reach Cmax (Tmax) of Selpercatinib in Plasma (Part 1)	PK: Tmax of Selpercatinib in plasma	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 (Part 1) for Total Radioactivity	PK: Tmax of [14C] Selpercatinib in plasma and whole blood	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma (Part 1)	PK: t½ of Selpercatinib in plasma	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 (Part 1) for Total Radioactivity	PK: t½ of [14C] Selpercatinib in plasma and whole blood	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Apparent Systemic Clearance (CL/F) of Selpercatinibin Plasma (Part 1)	PK: CL/F of Selpercatinib in plasma	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Selpercatinib in Plasma (Part 1)	PK: Vz/F of Selpercatinib in plasma	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Plasma Selpercatinib/Total Radioactivity AUC0-24 Ratio (Part 1)	PK: AUC0-24 of Selpercatinib in plasma/AUC0-24 of total radioactivity in plasma	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose
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 whole blood	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose
PK: AUClast of Selpercatinib in Plasma (Part 2)	PK: AUClast of Selpercatinib in plasma	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 (Part 2)	PK: AUClast of [14C] Selpercatinib in plasma	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 (Part 2)	PK: AUC0-inf of Selpercatinib in plasma	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 (Part 2)	PK: AUC0-inf of [14C] Selpercatinib in plasma	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 (Part 2)	PK: Cmax of Selpercatinib in plasma	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 (Part 2)	PK: Cmax of [14C] Selpercatinib in plasma	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 (Part 2)	PK: Tmax of Selpercatinib in plasma	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 (Part 2)	PK: Tmax of [14C] Selpercatinib in plasma	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 (Part 2)	PK: t½ of Selpercatinib in plasma	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 (Part 2)	PK: t½ of [14C] Selpercatinib in plasma	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 (Part 2)	PK: CL/F of Selpercatinib in plasma	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Systemic Clearance (CL) of [14C] Selpercatinib in Plasma (Part 2)	PK: CL of [14C] Selpercatinib in plasma	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 (Part 2)	PK: Vz/F of Selpercatinib in plasma	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
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	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Absolute Bioavailability (F) of Selpercatinib in Plasma (Part 2)	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.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: Study Director: 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), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): September 24, 2018
• Study Completion (Actual): September 24, 2018

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 4, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 17768; J2G-OX-JZJT (Other Identifier: Eli Lilly and Company); LOXO-RET-18016 (Other Identifier: Loxo Oncology, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No