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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05469100
• Collaborator: Loxo Oncology, Inc. (Industry)
• Enrollment: 37
• Locations: 6
• Arms: 4
• Actual Duration (Months): 7.6
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy; Renal Insufficiency	Drug: Selpercatinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Dec 19, 2018
• Actual Primary Completion Date: Aug 7, 2019
• Actual Study Completion Date: Aug 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Selpercatinib (Healthy participants) Single oral dose of Selpercatinib administered in a fasted state to participants with normal renal function.	Drug: Selpercatinib; Administered orally; Other Names: LY3527723 LOXO-292
Experimental: Cohort 2: Selpercatinib (Participants with mild renal impairment) Single oral dose of Selpercatinib administered in a fasted state to participants with mild renal impairment.	Drug: Selpercatinib; Administered orally; Other Names: LY3527723 LOXO-292
Experimental: Cohort 3: Selpercatinib (Participants with moderate renal impairment) Single oral dose of Selpercatinib administered in a fasted state to participants with moderate renal impairment.	Drug: Selpercatinib; Administered orally; Other Names: LY3527723 LOXO-292
Experimental: Cohort 4: Selpercatinib (Participants with severe renal impairment) Single oral dose of Selpercatinib administered in a fasted state to participants with severe renal impairment and not on dialysis.	Drug: Selpercatinib; Administered orally; Other Names: LY3527723 LOXO-292

Outcome Measures

Primary Outcome Measures

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

   PK: AUC0-t of Selpercatinib

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

   PK: AUC0-24 of Selpercatinib

3. PK: Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) of Selpercatinib [0 to up to 168 hours post-dose]

   PK: AUC0-inf of Selpercatinib

4. PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Selpercatinib [0 to up to 168 hours post-dose]

   PK: AUC%extrap of Selpercatinib

5. PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Selpercatinib [0 to up to 168 hours post-dose]

   PK: CL/F of Selpercatinib

6. PK: Maximum observed concentration (Cmax) of Selpercatinib [0 to up to 168 hours post-dose]

   PK: Cmax of Selpercatinib

7. PK: Time to reach Cmax (Tmax) of Selpercatinib [0 to up to 168 hours post-dose]

   PK: Tmax of Selpercatinib

8. PK: Apparent first order terminal elimination rate constant (Kel) of Selpercatinib [0 to up to 168 hours post-dose]

   PK: Kel of Selpercatinib

9. PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib [0 to up to 168 hours post-dose]

   PK: t½ of Selpercatinib

10. PK: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F) of Selpercatinib [0 to up to 168 hours post-dose]

    PK: Vz/F of Selpercatinib

11. PK: Total amount of drug excreted in the urine over the entire period of sample collection (Ae) of Selpercatinib [0 to up to 168 hours post-dose]

    PK: Ae of Selpercatinib

12. PK: Fraction of drug excretion during each collection interval (Fe) of Selpercatinib [0 to up to 168 hours post-dose]

    PK: Fe of Selpercatinib

13. PK: Renal clearance (CLr) of Selpercatinib [0 to up to 168 hours post-dose]

    PK: CLr of Selpercatinib

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anaheim Regional Center	Anaheim	California	United States	92801
2	Stanford Health Care, Valley Care Program	Pleasanton	California	United States	94588
3	Orange County Research Center	Tustin	California	United States	92780
4	Riverside Clinical Research	Edgewater	Florida	United States	32132
5	Clinical Pharmacology of Miami	Miami	Florida	United States	33014
6	Orlando Clinical Research Center	Orlando	Florida	United States	32809

Sponsors and Collaborators

• Eli Lilly and Company
• Loxo Oncology, Inc.

Investigators

• Study Director: 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT05469100
• Other Study ID Numbers: 17484; J2G-OX-JZJE; LOXO-RET-18023
• First Posted: Jul 21, 2022
• Last Update Posted: Jul 21, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Renal Insufficiency

Study Results

No Results Posted as of Jul 21, 2022