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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy, Renal Insufficiency

Intervention / Treatment
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* Drug: Selpercatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Selpercatinib (Healthy participants)<br>Single oral dose of Selpercatinib administered in a fasted state to participants with normal renal function. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;|
| Experimental: Cohort 2: Selpercatinib (Participants with mild renal impairment)<br>Single oral dose of Selpercatinib administered in a fasted state to participants with mild renal impairment. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;|
| Experimental: Cohort 3: Selpercatinib (Participants with moderate renal impairment)<br>Single oral dose of Selpercatinib administered in a fasted state to participants with moderate renal impairment. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;|
| Experimental: Cohort 4: Selpercatinib (Participants with severe renal impairment)<br>Single oral dose of Selpercatinib administered in a fasted state to participants with severe renal impairment and not on dialysis. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;|

What is the study measuring?
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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 | PK: AUC0-t of Selpercatinib | 0 to up to 168 hours post-dose | 
| 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 | 
| 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 | 
| PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Selpercatinib | PK: AUC%extrap of Selpercatinib | 0 to up to 168 hours post-dose | 
| 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 | 
| PK: Maximum observed concentration (Cmax) of Selpercatinib | PK: Cmax of Selpercatinib | 0 to up to 168 hours post-dose | 
| PK: Time to reach Cmax (Tmax) of Selpercatinib | PK: Tmax of Selpercatinib | 0 to up to 168 hours post-dose | 
| PK: Apparent first order terminal elimination rate constant (Kel) of Selpercatinib | PK: Kel of Selpercatinib | 0 to up to 168 hours post-dose | 
| PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib | PK: t½ of Selpercatinib | 0 to up to 168 hours post-dose | 
| 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 | 
| 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 | 
| PK: Fraction of drug excretion during each collection interval (Fe) of Selpercatinib | PK: Fe of Selpercatinib | 0 to up to 168 hours post-dose | 
| PK: Renal clearance (CLr) of Selpercatinib | PK: CLr of Selpercatinib | 0 to up to 168 hours post-dose |