A Study of Effect of Selpercatinib (LY3527723) in Participants With Normal and Impaired Renal Function
- Registration Number
- NCT05469100
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Selpercatinib (Control; Normal Renal Function) Selpercatinib 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. Selpercatinib (Mild Renal Impairment) Selpercatinib 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. Selpercatinib (Moderate Renal Impairment) Selpercatinib 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. Selpercatinib (Severe Renal Impairment) Selpercatinib 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.
- Primary Outcome Measures
Name Time Method Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma 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: AUC0-t of Selpercatinib
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma 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: AUC0-inf of Selpercatinib
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma 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 was calculated as (1 - AUC0-t/AUC0-inf) \* 100.
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma 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: Cmax of Selpercatinib
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma 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: Tmax of Selpercatinib
PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma 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 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).
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma 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: t½ of Selpercatinib.
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma 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: CL/F of Selpercatinib
PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma 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: Vz/F of Selpercatinib
PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma 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 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.
PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma 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 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.
PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma 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 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.
PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma 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 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.
PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma 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 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.
PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose PK: CumAe was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose PK: Cum%Dose was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
PK: Renal Clearance (CLr) of Selpercatinib in Urine Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (6)
Anaheim Regional Center
🇺🇸Anaheim, California, United States
Stanford Health Care, Valley Care Program
🇺🇸Pleasanton, California, United States
Orange County Research Center
🇺🇸Tustin, 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
Anaheim Regional Center🇺🇸Anaheim, California, United States