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

NCT05469100 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 17484J2G-OX-JZJELOXO-RET-18023
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Healthy; Renal Insufficiency

Outcome Measures

Primary Outcomes (17)

• 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

Study Arms (4)

Selpercatinib (Control; Normal Renal Function)

EXPERIMENTAL

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

Selpercatinib (Mild Renal Impairment)

EXPERIMENTAL

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

Selpercatinib (Moderate Renal Impairment)

EXPERIMENTAL

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

Selpercatinib (Severe Renal Impairment)

EXPERIMENTAL

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

Interventions

Selpercatinib DRUG

Administered orally

Also known as: LY3527723, LOXO-292

Selpercatinib (Control; Normal Renal Function); Selpercatinib (Mild Renal Impairment); Selpercatinib (Moderate Renal Impairment); Selpercatinib (Severe Renal Impairment)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (6)

Anaheim Regional Center

Anaheim, California, 92801, United States

Location

Stanford Health Care, Valley Care Program

Pleasanton, California, 94588, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

selpercatinib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 21, 2022
• Study Start: December 19, 2018
• Primary Completion: August 7, 2019
• Study Completion: August 7, 2019
• Last Updated: September 18, 2025
• Results First Posted: September 18, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)