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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05630287
• Other study ID #: 17768
• Secondary ID: J2G-OX-JZJTLOXO-
• Status: Completed
• Phase: Phase 1
• Start date: August 1, 2018
• Est. completion date: September 24, 2018

Study information

• Verified date: November 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 24, 2018
• Est. primary completion date: September 24, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• [14C] Selpercatinib
Administered as an oral solution
• Selpercatinib
Administered orally
• [14C] Selpercatinib
Administered intravenously

Locations

Country	Name	City	State
United States	LabCorp CRU, Inc.	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	PK: AUClast of Selpercatinib in plasma (Part 2)	PK: AUClast of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: AUClast of [14C] Selpercatinib in plasma (Part 2)	PK: AUClast of [14C] Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: AUC0-inf of Selpercatinib in plasma (Part 2)	PK: AUC0-inf of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	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
Primary	PK: Cmax of Selpercatinib in plasma (Part 2)	PK: Cmax of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: Cmax of [14C] Selpercatinib in plasma (Part 2)	PK: Cmax of [14C] Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: Tmax of Selpercatinib in plasma (Part 2)	PK: Tmax of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: Tmax of [14C] Selpercatinib in plasma (Part 2)	PK: Tmax of [14C] Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: t½ of Selpercatinib in plasma (Part 2)	PK: t½ of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: t½ of [14C] Selpercatinib in plasma (Part 2)	PK: t½ of [14C] Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	PK: CL/F of Selpercatinib in plasma (Part 2)	PK: CL/F of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	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
Primary	PK: Vz/F of Selpercatinib in plasma (Part 2)	PK: Vz/F of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose
Primary	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
Primary	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
Primary	PK: Absolute bioavailability (F) of Selpercatinib in plasma (Part 2)	PK: F of Selpercatinib in plasma	Pre-dose up to 168 hour post-dose