Clinical trial NCT05436912: A Study of Effects of Selpercatinib in Hepatically Impaired Participants and Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Hepatic Impairment
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Loxo Oncology, Inc.
First posted: 2022-06-29
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib
timeFrame: 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
measure: PK: Time to Reach Cmax (Tmax) of Selpercatinib
timeFrame: 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
measure: PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib
timeFrame: 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
measure: PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib
timeFrame: 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
measure: PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib
timeFrame: 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
measure: PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib
timeFrame: 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
measure: PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib
timeFrame: 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
measure: PK: Apparent Systemic Clearance (CL/F) of Selpercatinib
timeFrame: 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
measure: PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib
timeFrame: 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
measure: PK: Mean Residence Time (MRT) of Selpercatinib
timeFrame: 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
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline up to Week 7
Secondary outcomes:
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Orange County Research Institute
state: California
city: Monterey Park
country: United States
facility: National Institute of Clinical Research
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: San Antonio
country: United States
facility: The Texas Liver Institute
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: