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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy, Hepatic Impairment

Intervention / Treatment
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* Drug: Selpercatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy participants with normal hepatic function<br>Selpercatinib administered orally to healthy participants. | Drug: Selpercatinib<br>* Administered orally.<br>* Other names: LOXO-292;|
| Experimental: Participants with mild hepatic impairment<br>Selpercatinib administered orally to participants with mild hepatic impairment per Child-Pugh [CP] classification (CP Class A, score of 5 or 6). | Drug: Selpercatinib<br>* Administered orally.<br>* Other names: LOXO-292;|
| Experimental: Participants with moderate hepatic impairment<br>Selpercatinib administered orally to participants with mild hepatic impairment per CP classification (CP Class C, score of 10 to 15). | Drug: Selpercatinib<br>* Administered orally.<br>* Other names: LOXO-292;|
| Experimental: Participants with severe hepatic impairment<br>Selpercatinib administered orally to participants with mild hepatic impairment per CP classification (CP Class B, score of 7 to 9)). | Drug: Selpercatinib<br>* Administered orally.<br>* Other names: LOXO-292;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum observed concentration (Cmax) of Selpercatinib | Cmax of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Time to reach Cmax (Tmax) of Selpercatinib | Tmax of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Area under the concentration-time curve (AUC), from time 0 to the last observed non-zero concentration (AUC0-t) of Selpercatinib | AUC0-t of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: AUC extrapolated to infinity (AUC0-∞) of Selpercatinib | AUC0-∞ of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Percentage extrapolation for AUC (%AUCextrap) of Selpercatinib | %AUCextrap of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Apparent terminal elimination rate constant (λz) of Selpercatinib | λz of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Apparent terminal elimination half-life (t1/2) of Selpercatinib | t1/2 of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Apparent systemic clearance (CL/F) of Selpercatinib | CL/F of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Apparent volume of distribution during the terminal phase (Vd/F) of Selpercatinib | Vd/F of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| PK: Mean residence time (MRT) of Selpercatinib | MRT of Selpercatinib | Pre-dose up to 240 hour post-dose (Days 1-11) | 
| Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module. | Baseline through Week 7 |