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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05436912
• Collaborator: Loxo Oncology, Inc. (Industry)
• Enrollment: 25
• Locations: 7
• Arms: 4
• Actual Duration (Months): 10.6
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy; Hepatic Impairment	Drug: Selpercatinib	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Dec 10, 2018
• Actual Primary Completion Date: Oct 4, 2019
• Actual Study Completion Date: Oct 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy participants with normal hepatic function Selpercatinib administered orally to healthy participants.	Drug: Selpercatinib; Administered orally.; Other Names: LY3527723 LOXO-292
Experimental: Participants with mild hepatic impairment Selpercatinib administered orally to participants with mild hepatic impairment per Child-Pugh [CP] classification (CP Class A, score of 5 or 6).	Drug: Selpercatinib; Administered orally.; Other Names: LY3527723 LOXO-292
Experimental: Participants with moderate hepatic impairment Selpercatinib administered orally to participants with mild hepatic impairment per CP classification (CP Class C, score of 10 to 15).	Drug: Selpercatinib; Administered orally.; Other Names: LY3527723 LOXO-292
Experimental: Participants with severe hepatic impairment Selpercatinib administered orally to participants with mild hepatic impairment per CP classification (CP Class B, score of 7 to 9)).	Drug: Selpercatinib; Administered orally.; Other Names: LY3527723 LOXO-292

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum observed concentration (Cmax) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   Cmax of Selpercatinib

2. PK: Time to reach Cmax (Tmax) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   Tmax of Selpercatinib

3. PK: Area under the concentration-time curve (AUC), from time 0 to the last observed non-zero concentration (AUC0-t) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   AUC0-t of Selpercatinib

4. PK: AUC extrapolated to infinity (AUC0-∞) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   AUC0-∞ of Selpercatinib

5. PK: Percentage extrapolation for AUC (%AUCextrap) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   %AUCextrap of Selpercatinib

6. PK: Apparent terminal elimination rate constant (λz) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   λz of Selpercatinib

7. PK: Apparent terminal elimination half-life (t1/2) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   t1/2 of Selpercatinib

8. PK: Apparent systemic clearance (CL/F) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   CL/F of Selpercatinib

9. PK: Apparent volume of distribution during the terminal phase (Vd/F) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

   Vd/F of Selpercatinib

10. PK: Mean residence time (MRT) of Selpercatinib [Pre-dose up to 240 hour post-dose (Days 1-11)]

    MRT of Selpercatinib

11. Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [Baseline through Week 7]

    A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Orange County Research Institute	Anaheim	California	United States	92801
2	National Institute of Clinical Research	Monterey Park	California	United States	91754
3	Orange County Research Center	Tustin	California	United States	92780
4	Riverside Clinical Research	Edgewater	Florida	United States	32132
5	Clinical Pharmacology of Miami	Miami	Florida	United States	33014
6	Orlando Clinical Research Center	Orlando	Florida	United States	32809
7	The Texas Liver Institute	San Antonio	Texas	United States	78215

Sponsors and Collaborators

• Eli Lilly and Company
• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT05436912
• Other Study ID Numbers: 17483; J2G-OX-JZJD; LOXO-RET-18022
• First Posted: Jun 29, 2022
• Last Update Posted: Jun 29, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Jun 29, 2022