A Study of Effects of Selpercatinib in Hepatically Impaired Participants and Healthy Participants
- Registration Number
- NCT05436912
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
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Female participants of non-childbearing potential who are agreeable to take birth control measures until study completion
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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.
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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
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Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study
- 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- Have previously participated or withdrawn from this study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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 160 milligram (mg) Selpercatinib: Normal Hepatic Function Selpercatinib 160 mg selpercatinib administered orally to healthy participants after at least a 2-hour fast on Day 1. 160 mg Selpercatinib: Mild Hepatic Impairment Selpercatinib 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. 160 mg Selpercatinib: Moderate Hepatic Impairment Selpercatinib 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. 160 mg Selpercatinib: Severe Hepatic Impairment Selpercatinib 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.
- Primary Outcome Measures
Name Time Method PK: Time to Reach Cmax (Tmax) of Selpercatinib 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: Tmax of Selpercatinib was reported.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib 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: Cmax of selpercatinib was reported.
PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib 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: AUC0-t was calculated using the linear trapezoidal rule for increasing and decreasing concentrations.
PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib 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 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.
PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib 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: %AUCextrap of Selpercatinib was reported.
PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib 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, where λZ is the magnitude of the slope of the linear regression of the log concentration versus-time profile during the terminal phase.
PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib 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 (whenever possible), where t1/2 = natural log (ln)(2)/λZ.
PK: Apparent Systemic Clearance (CL/F) of Selpercatinib 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 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).
PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib 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: Vd/F was calculated as CL/F/λZ.
PK: Mean Residence Time (MRT) of Selpercatinib 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: MRT represents the average time the drug (selpercatinib) stays in the body.
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration Baseline up to Week 7 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (7)
Orange County Research Center
🇺🇸Tustin, California, United States
Orange County Research Institute
🇺🇸Anaheim, California, United States
Riverside Clinical Research
🇺🇸Edgewater, Florida, United States
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States
National Institute of Clinical Research
🇺🇸Monterey Park, California, United States
The Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Clinical Pharmacology of Miami
🇺🇸Miami, Florida, United States