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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Renal Insufficiency
• Intervention / Treatment: Drug: Selpercatinib

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Regional Center
    • Pleasanton, California, United States, 94588
      • Stanford Health Care, Valley Care Program
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selpercatinib (Control; Normal Renal Function); Participants with normal renal function (estimated glomerular filtration rate greater than or equal to [eGFR ≥ 90 milliliters per minute (mL/min) per 1.73 square meters (m²)] received a single 160 milligrams (mg) oral dose of Selpercatinib on Day 1, administered in a fasted state.	Drug: Selpercatinib; Administered orally; Other Names: LOXO-292; LY3527723
Experimental: Selpercatinib (Mild Renal Impairment); Participants with mild renal impairment (eGFR between 60 and 90 mL/min/1.73 m²) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state.	Drug: Selpercatinib; Administered orally; Other Names: LOXO-292; LY3527723
Experimental: Selpercatinib (Moderate Renal Impairment); Participants with moderate renal impairment (eGFR between 30 and 60 mL/min/1.73 m²) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state.	Drug: Selpercatinib; Administered orally; Other Names: LOXO-292; LY3527723
Experimental: Selpercatinib (Severe Renal Impairment); Participants with severe renal impairment (eGFR less than (<) 30 mL/min/1.73 m² and not requiring hemodialysis) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state.	Drug: Selpercatinib; Administered orally; Other Names: LOXO-292; LY3527723

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma	PK: AUC0-t of Selpercatinib	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma	PK: AUC0-inf of Selpercatinib	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma	PK: Percentage of AUC0-inf extrapolated was calculated as (1 - AUC0-t/AUC0-inf) * 100.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma	PK: Cmax of Selpercatinib	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma	PK: Tmax of Selpercatinib	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma	PK: Apparent terminal elimination rate constant; represents the fraction of drug eliminated per unit time calculated by linear least squares regression analysis using the maximum number of points in the terminal log linear phase (e.g., three or more non zero plasma concentrations).	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma	PK: t½ of Selpercatinib.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma	PK: CL/F of Selpercatinib	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma	PK: Vz/F of Selpercatinib	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma	AUC0-t,u was calculated by multiplying AUC0-t by Fu (i.e., AUC0-t*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma	AUC0-inf,u was calculated by multiplying AUC0-inf by Fu (i.e., AUC0-inf*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma	Cmax,u was calculated by multiplying Cmax by Fu (i.e., Cmax*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma	CL/F,u was calculated by multiplying CL/F by Fu (i.e., CL/F*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma	Vz/F,u was calculated by multiplying Vz/F by Fu (i.e., Vz/F*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine	PK: CumAe was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.	Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose
PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine	PK: Cum%Dose was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.	Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose
PK: Renal Clearance (CLr) of Selpercatinib in Urine	PK: CLr of Selpercatinib was reported.The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.	Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: 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 record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Actual): August 7, 2019
• Study Completion (Actual): August 7, 2019

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; selpercatinib
• Other Study ID Numbers: 17484; J2G-OX-JZJE (Other Identifier: Eli Lilly and Company); LOXO-RET-18023 (Other Identifier: Loxo Oncology, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No