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

NCT05436912 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 17483J2G-OX-JZJDLOXO-RET-18022
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Healthy; Hepatic Impairment

Outcome Measures

Primary Outcomes (11)

• 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

Study Arms (4)

160 milligram (mg) Selpercatinib: Normal Hepatic Function

EXPERIMENTAL

160 mg selpercatinib administered orally to healthy participants after at least a 2-hour fast on Day 1.

Drug: Selpercatinib

160 mg Selpercatinib: Mild Hepatic Impairment

EXPERIMENTAL

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

160 mg Selpercatinib: Moderate Hepatic Impairment

EXPERIMENTAL

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

160 mg Selpercatinib: Severe Hepatic Impairment

EXPERIMENTAL

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

Interventions

Selpercatinib DRUG

Administered orally.

Also known as: LY3527723, LOXO-292

160 mg Selpercatinib: Mild Hepatic Impairment; 160 mg Selpercatinib: Moderate Hepatic Impairment; 160 mg Selpercatinib: Severe Hepatic Impairment; 160 milligram (mg) Selpercatinib: Normal Hepatic Function

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (7)

Orange County Research Institute

Anaheim, California, 92801, United States

Location

National Institute of Clinical Research

Monterey Park, California, 91754, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Interventions

selpercatinib

Results Point of Contact

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

ClinicalTrials.gov@lilly.com

800-545-5979

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: June 24, 2022
• First Posted: June 29, 2022
• Study Start: December 10, 2018
• Primary Completion: October 4, 2019
• Study Completion: October 30, 2019
• Last Updated: April 13, 2025
• Results First Posted: April 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)