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

Merck Sharp & Dohme LLC18 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Renal Impairment

Interventions

MK-8527DRUG

Oral Capsule

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Research by Design ( Site 0001)

Chicago, Illinois, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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).

Time frame: Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose