A Study of Effects of Selpercatinib in Hepatically Impaired Participants and Healthy Participants

Open-label, Nonrandomized, Single-dose, Parallel-group, Safety, Tolerance, and Pharmacokinetic Study of LOXO-292 Administered to Fasted Hepatically Impaired Male and Female Subjects and Fasted Matched-control Healthy Subjects

The main purpose of this study is to assess how selpercatinib gets into the blood stream and how long it takes the body to remove it when administered to participants with impaired hepatic function compared to healthy participants. Information about safety and tolerability will be collected. The study will last up to about 7 weeks, inclusive of screening period.

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: Selpercatinib

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Orange County Research Institute
    • Monterey Park, California, United States, 91754
      • National Institute of Clinical Research
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • The Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female participants of non-childbearing potential who are agreeable to take birth control measures until study completion

• Males who are capable of fathering a child must agree to use one of the following methods of contraception from the time of the dose administration through 6 months after dose administration:

  • Male sterilization, with documented confirmation of surgical success. Male subjects will be surgically sterile for at least 90 days prior to Check-in (Day -1). If documentation is not available, male subjects must follow one of the contraception methods below:
  • Male condom with spermicide, or
  • For a female partner of male study participant:
  • Intrauterine device (IUD) (hormonal IUD; eg, Mirena®). Copper IUDs are acceptable (eg, ParaGard®);
  • Established use of oral, implanted, transdermal, or hormonal method of contraception associated with inhibition of ovulation; or
  • Bilateral tubal ligation.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²) and had a minimum weight of at least 50 kg at screening
• Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study

Exclusion Criteria:

• Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study
• Have previously participated or withdrawn from this study
• Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study
• Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening
• Require treatment with inducers or inhibitors of cytochrome P450 (CYP) CYP3A within 14 days before the first dose of study drug through the end of treatment or early termination

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 160 milligram (mg) Selpercatinib: Normal Hepatic Function; 160 mg selpercatinib administered orally to healthy participants after at least a 2-hour fast on Day 1.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723
Experimental: 160 mg Selpercatinib: Mild Hepatic Impairment; 160 mg selpercatinib administered orally to participants with mild hepatic impairment per Child-Pugh [CP] classification (CP Class A, score of 5 or 6) after at least a 2-hour fast on Day 1.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723
Experimental: 160 mg Selpercatinib: Moderate Hepatic Impairment; 160 mg selpercatinib administered orally to participants with moderate hepatic impairment per CP classification (CP Class B, score of 7 to 9) after at least a 2-hour fast on Day 1.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723
Experimental: 160 mg Selpercatinib: Severe Hepatic Impairment; 160 mg Selpercatinib administered orally to participants with severe hepatic impairment per CP classification (CP Class C, score of 10 to 15) after at least a 2-hour fast on Day 1.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib	PK: Cmax of selpercatinib was reported.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Time to Reach Cmax (Tmax) of Selpercatinib	PK: Tmax of Selpercatinib was reported.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib	PK: AUC0-t was calculated using the linear trapezoidal rule for increasing and decreasing concentrations.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib	PK: Area under the plasma concentration time curve extrapolated to infinity, calculated as AUC(0-t) + Ct/λZ, where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib	PK: %AUCextrap of Selpercatinib was reported.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib	PK: Apparent terminal elimination rate constant, where λZ is the magnitude of the slope of the linear regression of the log concentration versus-time profile during the terminal phase.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib	PK: Apparent terminal elimination half-life (whenever possible), where t1/2 = natural log (ln)(2)/λZ.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Apparent Systemic Clearance (CL/F) of Selpercatinib	CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr).	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib	PK: Vd/F was calculated as CL/F/λZ.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
PK: Mean Residence Time (MRT) of Selpercatinib	PK: MRT represents the average time the drug (selpercatinib) stays in the body.	Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.	Baseline up to Week 7

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): December 10, 2018
• Primary Completion (Actual): October 4, 2019
• Study Completion (Actual): October 30, 2019

Study Registration Dates

• First Submitted: June 24, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 17483 (Other Identifier: City of Hope Medical Center); J2G-OX-JZJD (Other Identifier: Eli Lilly and Company); LOXO-RET-18022 (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