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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05630287

Enrollment

Registered

2022-11-29

Start date

2018-08-01

Completion date

2018-09-24

Last updated

2025-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

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.

Interventions

DRUG[14C]-Selpercatinib

Administered as an oral solution

DRUGSelpercatinib

Administered orally

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 55 Years

Healthy volunteers

Yes

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)

Design outcomes

Primary

Measure	Time frame	Description
PK: Tmax of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity	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
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma (Part 1)	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
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: 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 Selpercatinib in plasma
PK: AUClast of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity	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
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma (Part 1)	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 Selpercatinib in plasma
PK: AUC0-inf of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity	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
PK: Area Under the Concentration-time Curve, From Time 0 to Hour 24 (AUC0-24) of Selpercatinib in Plasma (Part 1)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose	PK: AUC0-24 of Selpercatinib in plasma
PK: (AUC0-24) of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity	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
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma (Part 1)	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
PK: Cmax of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity	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
PK: Time to Reach Cmax (Tmax) of Selpercatinib in Plasma (Part 1)	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
PK: t½ of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity	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
PK: Apparent Systemic Clearance (CL/F) of Selpercatinibin Plasma (Part 1)	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
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Selpercatinib in Plasma (Part 1)	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
PK: Plasma Selpercatinib/Total Radioactivity AUC0-24 Ratio (Part 1)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose	PK: AUC0-24 of Selpercatinib in plasma/AUC0-24 of total radioactivity in plasma
PK: Blood/Plasma Total Radioactivity AUC0-24 Ratio (Part 1)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose	PK: AUC0-24 of total radioactivity in whole blood/AUC0-24 of total radioactivity in whole blood
PK: AUClast of Selpercatinib in Plasma (Part 2)	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 Selpercatinib in plasma
PK: AUClast of [14C] Selpercatinib in Plasma (Part 2)	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
PK: AUC0-inf of Selpercatinib in Plasma (Part 2)	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
PK: AUC0-inf of [14C] Selpercatinib in Plasma (Part 2)	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
PK: Cmax of Selpercatinib in Plasma (Part 2)	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
PK: Cmax of [14C] Selpercatinib in Plasma (Part 2)	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
PK: Tmax of Selpercatinib in Plasma (Part 2)	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
PK: Tmax of [14C] Selpercatinib in Plasma (Part 2)	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
PK: t½ of Selpercatinib in Plasma (Part 2)	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
PK: t½ of [14C] Selpercatinib in Plasma (Part 2)	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
PK: CL/F of Selpercatinib in Plasma (Part 2)	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
PK: Systemic Clearance (CL) of [14C] Selpercatinib in Plasma (Part 2)	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 of \[14C\] Selpercatinib in plasma
PK: Vz/F of Selpercatinib in Plasma (Part 2)	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
PK: Volume of Distribution During the Terminal Phase (Vz) of [14C] Selpercatinib in Plasma (Part 2)	Pre-dose up to 168 hour post-dose	PK: Vz of \[14C\] Selpercatinib in plasma
PK: Volume of Distribution at Steady State (Vss) of [14C] Selpercatinib in Plasma (Part 2)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose	PK: Vss of \[14C\] Selpercatinib in plasma
PK: Absolute Bioavailability (F) of Selpercatinib in Plasma (Part 2)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose	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.

Countries

United States

Participant flow

Pre-assignment details

Participants in Part 1 did not participate in Part 2, nor did participants in Part 2 participate in Part 1. Parts 1 and 2 were independent of each other and did not need to be conducted in sequential order.

Participants by arm

Arm	Count
Carbon-14-labelled [14C]-Selpercatinib - Part 1 Participants received a single oral dose of 165 milligram (mg) of \[14C\]-Selpercatinib (containing approximately 40 µCi).	6
Selpercatinib and [14C]-Selpercatinib - Part 2 Participants received a single oral dose of 160 mg Selpercatinib followed by a single dose of \<100 µg of \[14C\]-Selpercatinib (containing approximately 1 µCi) administered intravenously (IV).	6
Total	12

Baseline characteristics

Characteristic	Carbon-14-labelled [14C]-Selpercatinib - Part 1	Total	Selpercatinib and [14C]-Selpercatinib - Part 2
Age, Continuous	35 years STANDARD_DEVIATION 12.5	34 years STANDARD_DEVIATION 9.6	32 years STANDARD_DEVIATION 6.2
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	2 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	10 Participants	5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	4 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	8 Participants	4 Participants
Region of Enrollment United States	6 participants	12 participants	6 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	6 Participants	12 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 6
other Total, other adverse events	4 / 6	1 / 6
serious Total, serious adverse events	0 / 6	0 / 6

Outcome results

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

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