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

NCT05630287 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 17768J2G-OX-JZJTLOXO-RET-18016
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (32)

• 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

Study Arms (2)

Carbon-14-labelled [14C]-Selpercatinib - Part 1

EXPERIMENTAL

Participants received a single oral dose of 165 milligram (mg) of \[14C\]-Selpercatinib (containing approximately 40 µCi).

Drug: [14C]-Selpercatinib

Selpercatinib and [14C]-Selpercatinib - Part 2

EXPERIMENTAL

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; Drug: [14C]-Selpercatinib

Interventions

[14C]-Selpercatinib DRUG

Administered as an oral solution

Also known as: LY3527723, LOXO-292

Carbon-14-labelled [14C]-Selpercatinib - Part 1

Selpercatinib DRUG

Administered orally

Also known as: LY3527723, LOXO-292

Selpercatinib and [14C]-Selpercatinib - Part 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (1)

LabCorp CRU, Inc.

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

selpercatinib

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

8005955979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: November 29, 2022
• Study Start: August 1, 2018
• Primary Completion: September 24, 2018
• Study Completion: September 24, 2018
• Last Updated: April 23, 2025
• Results First Posted: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)