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

Eli Lilly and Company12 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

[14C]-SelpercatinibDRUG

Administered as an oral solution

SelpercatinibDRUG

Administered orally

[14C]-SelpercatinibDRUG

Administered intravenously

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

LabCorp CRU, Inc.

Madison, Wisconsin, United States

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose

Data from ClinicalTrials.gov

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PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma (Part 1)

PK: Cmax of Selpercatinib in plasma

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose