A Study of Effect of Selpercatinib (LY3527723) in Participants With Normal and Impaired Renal Function

Healthy Clinical Trial

Official title:

A Phase 1, Open-Label, Parallel-Cohort, Single-Dose Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics of LOXO-292

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05469100
• Other study ID #: 17484
• Secondary ID: J2G-OX-JZJELOXO-
• Status: Completed
• Phase: Phase 1
• Start date: December 19, 2018
• Est. completion date: August 7, 2019

Study information

• Verified date: July 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to assess the amount of study drug that reaches the bloodstream and the time it takes for the body to get rid of it when given to participants with renal (kidney) impairment compared to healthy participants. The study will last up to 9 days, excluding screening.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: August 7, 2019
• Est. primary completion date: August 7, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

For all participants:

• Body mass index (BMI) = 18.0 and = 40.0 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

• Female of non childbearing potential: must have undergone sterilization procedures at least 6 months prior to the Screening

• Males who are capable of fathering a child must agree to use contraception from the time of the dose administration through 6 months after the last dose

For renal participants:

• Participant has stable renal disease status and function at least 1 month prior to LOXO-292 administration.

• Participant is not currently or has not previously being on hemodialysis

• Baseline estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease (MDRD) equation at screening as follows:

• Severe Renal Impairment (RI): < 30 milliliter per minute (mL/min)/1.73m²

• Moderate RI: = 30 and < 60 mL/min/1.73m²

• Mild RI: = 60 and < 90 mL/min/1.73m²

The MDRD equation is as follows (for females multiply result by 0.742, if African American multiply result by 1.212):

eGFR = 175 x [serum creatinine in milligrams per deciliter (mg/dL) measured with a standardized assay]^-1.154 x (Age)^-0.203

Exclusion Criteria:

For renal participants:

• Has rapidly fluctuating renal function, as determined by historical measurements; or has demonstrated or suspected renal artery stenosis. Rapidly fluctuating renal function is defined as creatinine clearance or eGFR that differs by more than 20% within at least 3 months of the screening creatinine clearance or eGFR. If historical measurements are not available, then the 2 screening measurements will be used to demonstrate stability.

• Participants who have had a renal transplant, a nephrectomy, or participants with a known history of nephrotic syndrome.

• Participants who have required new medication for renal disease within 30 days prior to Check-in

Related Conditions & MeSH terms

• Healthy
• Renal Insufficiency

Intervention

Drug:
• Selpercatinib
Administered orally

Locations

Country	Name	City	State
United States	Anaheim Regional Center	Anaheim	California
United States	Riverside Clinical Research	Edgewater	Florida
United States	Clinical Pharmacology of Miami	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Stanford Health Care, Valley Care Program	Pleasanton	California
United States	Orange County Research Center	Tustin	California

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK): Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Selpercatinib	PK: AUC0-t of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Area under the concentration-time curve, from time 0 to Hour 24 (AUC0-24) of Selpercatinib	PK: AUC0-24 of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) of Selpercatinib	PK: AUC0-inf of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Selpercatinib	PK: AUC%extrap of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Selpercatinib	PK: CL/F of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Maximum observed concentration (Cmax) of Selpercatinib	PK: Cmax of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Time to reach Cmax (Tmax) of Selpercatinib	PK: Tmax of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Apparent first order terminal elimination rate constant (Kel) of Selpercatinib	PK: Kel of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib	PK: t½ of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F) of Selpercatinib	PK: Vz/F of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Total amount of drug excreted in the urine over the entire period of sample collection (Ae) of Selpercatinib	PK: Ae of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Fraction of drug excretion during each collection interval (Fe) of Selpercatinib	PK: Fe of Selpercatinib	0 to up to 168 hours post-dose
Primary	PK: Renal clearance (CLr) of Selpercatinib	PK: CLr of Selpercatinib	0 to up to 168 hours post-dose