A Study of MK-8527 in Participants With Moderate and Severe Renal Impairment (MK-8527-008)

An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-8527 in Participants With Moderate and Severe Renal Impairment

The goal of this study is to evaluate the effect of moderate and severe renal impairment (RI) on the pharmacokinetics (PK), safety, and tolerability of MK-8527. There will be no hypothesis testing in the study.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: MK-8527

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

Moderate and Severe RI

• With the exception of RI, is in sufficient health for study participation.
• Has stable renal function.

Healthy

• Matches mean age to participants with moderate and severe RI.
• Has normal renal function.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

All participants

• History of cancer (malignancy).
• Positive test results for Human-immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV).
• Had a major surgery or lost significant volume of blood within 56 days prior to dosing.
• Donated plasma within 7 days prior to dosing.

Moderate and Severe RI

• Failed renal transplant or had a nephrectomy.
• End stage renal disease requiring dialysis.
• Any significant arrhythmia or conduction abnormality.
• Has non-sustained or sustained ventricular tachycardia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Renal Impairment; Participants with moderate renal impairment receive a single dose of MK-8527 on Day 1.	Drug: MK-8527; Oral Capsule
Experimental: Severe Renal Impairment; Participants with severe renal impairment receive a single dose of MK-8527 on Day 1.	Drug: MK-8527; Oral Capsule
Experimental: Healthy; Healthy participants receive a single dose of MK-8527 on Day 1.	Drug: MK-8527; Oral Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration Versus Time Curve From Time 0 to Last Quantifiable Sample (AUC0-last) of MK-8527 in Plasma	Blood samples were collected at pre-specified time points to determine the AUC0-last of MK-8527 in participant's plasma. AUC0 to last of MK-8527 was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration. AUC0-last was calculated using noncompartmental analysis.	Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of MK-8527 in Plasma	Blood samples were collected at pre-specified time points to determine the AUC0-inf of MK-8527 in participant's plasma. AUC0-inf was defined as AUC0-last + (Cest,last/λz) where Cest,last was the estimated last measurable concentration, and λz was the apparent first-order terminal elimination rate constant.	Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Maximum Concentration (Cmax) of MK-8527 in Plasma	Blood samples were collected at pre-specified time points to determine the Cmax of MK-8527 in participant's plasma. Cmax was defined as the maximum observed concentration of MK-8527 in plasma after the administration of a given dose.	Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Time to Maximum Concentration (Tmax) of MK-8527 in Plasma	Blood samples were collected at pre-specified time points to determine the tmax of MK-8527 in participant's plasma. Tmax of MK-8527 in plasma was determined by deriving the difference between the time of the blood draw associated with the Cmax and the time of study drug administration	Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Apparent Terminal Half-life (t1/2) of MK-8527 in Plasma	Blood samples were collected at pre-specified time points to determine the t1/2 of MK-8527 in participant's plasma. t1/2 was defined as 0.693/Apparent terminal elimination rate constant (λz).	Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Apparent Clearance (CL/F) of MK-8527 in Plasma	Blood samples were collected at pre-specified time points to determine the CL/F of MK-8527 in participant's plasma. CL/F was defined as dose/(AUC0-inf).	Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-8527 in Plasma	Blood samples were collected at pre-specified time points to determine the Vz/F of MK-8527 in participant's plasma. Vz/F of MK-8527 in plasma was determined using the formula Dose/(AUC0-inf × λz).	Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience One or More Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to approximately 29 days
Number of Participants Who Discontinue Study Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to approximately 29 days
AUC0-last of MK-8527-triphosphate (TP) in Peripheral Blood Mononuclear Cells (PBMCs)	Blood samples were collected at pre-specified time points to determine the AUC0-last of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. AUC0 to last of MK-8527 was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration.	Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose
AUC0-inf of MK-8527-TP in PBMCs	Blood samples were collected at pre-specified time points to determine the AUC0-inf of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. AUC0-inf was defined as AUC0-last + (Cest,last/λz) where Cest,last was the estimated last measurable concentration, and λz was the apparent first-order terminal elimination rate constant.	Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose
Cmax of MK-8527-TP in PBMCs	Blood samples were collected at pre-specified time points to determine the Cmax of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Cmax was defined as the maximum observed concentration of MK-8527-TP after the administration of a given dose.	Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose
Concentration at 168 Hours (C168) of MK-8527-TP in PBMCs	Blood samples were collected at pre-specified time points to determine the C168 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Geometric mean of C168 of MK-8527-TP in PBMCs was determined.	168 hours post dose
Concentration at 672 Hours (C672) of MK-8527-TP in PBMCs in Participants With Moderate and Severe Renal Impairment	Blood samples were collected at pre-specified time points to determine the C672 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Geometric mean of C672 of MK-8527-TP in PBMCs was determined.	672 hours post dose
C672 of MK-8527-TP in PBMCs in Healthy Participants	Blood samples were collected at pre-specified time points to determine the C672 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Since ≤ 50% of healthy participants had BLQ values, the BLQ value was set to zero and the median, minimum, and maximum was reported for C672.	672 hours post dose
Tmax of MK-8527-TP in PBMCs	Blood samples were collected at pre-specified time points to determine the Tmax of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Tmax of MK-8527-TP was determined by deriving the difference between the time of the blood draw associated with the Cmax and the time of study drug administration	Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose
T1/2 of MK-8527-TP in PBMCs	Blood samples were collected at pre-specified time points to determine the t1/2 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. t1/2 was defined as 0.693/Apparent terminal elimination rate constant (λz).	Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2024
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: February 29, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 6, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency
• Other Study ID Numbers: 8527-008; MK-8527-008 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No