Clinical trial NCT05469100: A Study of Effect of Selpercatinib (LY3527723) in Participants With Normal and Impaired Renal Function
Official title: A Phase 1, Open-Label, Parallel-Cohort, Single-Dose Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics of LOXO-292
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Renal Insufficiency
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Loxo Oncology, Inc.
First posted: 2022-07-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics (PK): Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Area under the concentration-time curve, from time 0 to Hour 24 (AUC0-24) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Maximum observed concentration (Cmax) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Time to reach Cmax (Tmax) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Apparent first order terminal elimination rate constant (Kel) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Total amount of drug excreted in the urine over the entire period of sample collection (Ae) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Fraction of drug excretion during each collection interval (Fe) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
measure: PK: Renal clearance (CLr) of Selpercatinib
timeFrame: 0 to up to 168 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Regional Center
state: California
city: Pleasanton
country: United States
facility: Stanford Health Care, Valley Care Program
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: