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

Phase 1
Completed
Conditions
Healthy
Renal Insufficiency
Interventions
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
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 1: Selpercatinib (Healthy participants)SelpercatinibSingle oral dose of Selpercatinib administered in a fasted state to participants with normal renal function.
Cohort 2: Selpercatinib (Participants with mild renal impairment)SelpercatinibSingle oral dose of Selpercatinib administered in a fasted state to participants with mild renal impairment.
Cohort 4: Selpercatinib (Participants with severe renal impairment)SelpercatinibSingle oral dose of Selpercatinib administered in a fasted state to participants with severe renal impairment and not on dialysis.
Cohort 3: Selpercatinib (Participants with moderate renal impairment)SelpercatinibSingle oral dose of Selpercatinib administered in a fasted state to participants with moderate renal impairment.
Primary Outcome Measures
NameTimeMethod
PK: Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) of Selpercatinib0 to up to 168 hours post-dose

PK: AUC0-inf of Selpercatinib

PK: Time to reach Cmax (Tmax) of Selpercatinib0 to up to 168 hours post-dose

PK: Tmax of Selpercatinib

PK: Apparent first order terminal elimination rate constant (Kel) of Selpercatinib0 to up to 168 hours post-dose

PK: Kel of Selpercatinib

PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib0 to up to 168 hours post-dose

PK: t½ of Selpercatinib

PK: Total amount of drug excreted in the urine over the entire period of sample collection (Ae) of Selpercatinib0 to up to 168 hours post-dose

PK: Ae of Selpercatinib

PK: Fraction of drug excretion during each collection interval (Fe) of Selpercatinib0 to up to 168 hours post-dose

PK: Fe of Selpercatinib

Pharmacokinetics (PK): Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Selpercatinib0 to up to 168 hours post-dose

PK: AUC0-t of Selpercatinib

PK: Area under the concentration-time curve, from time 0 to Hour 24 (AUC0-24) of Selpercatinib0 to up to 168 hours post-dose

PK: AUC0-24 of Selpercatinib

PK: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F) of Selpercatinib0 to up to 168 hours post-dose

PK: Vz/F of Selpercatinib

PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Selpercatinib0 to up to 168 hours post-dose

PK: CL/F of Selpercatinib

PK: Renal clearance (CLr) of Selpercatinib0 to up to 168 hours post-dose

PK: CLr of Selpercatinib

PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Selpercatinib0 to up to 168 hours post-dose

PK: AUC%extrap of Selpercatinib

PK: Maximum observed concentration (Cmax) of Selpercatinib0 to up to 168 hours post-dose

PK: Cmax of Selpercatinib

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (6)

Orange County Research Center

🇺🇸

Tustin, California, United States

Stanford Health Care, Valley Care Program

🇺🇸

Pleasanton, California, 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

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