The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050)

Phase 1CompletedNCT01937975

Merck Sharp & Dohme LLC24 enrolled

Overview

Grazoprevir (MK-5172) and Elbasvir (MK-8742) were studied as the principal components of combination oral therapy for hepatitis C virus (HCV). The study examined the pharmacokinetic (PK) profiles of Grazoprevir and Elbasvir following 10 days of dosing in participants with end stage renal disease (ESRD) on hemodialysis (HD) or participants with severe renal impairment. Both groups were compared to healthy matched controls.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Hepatitis C Renal Impairment

Interventions

GrazoprevirDRUG

100 mg oral tablet administered once a day for 10 days

ElbasvirDRUG

50 mg oral tablet administered once a day for 10 days

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: All Participants * For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or be using an acceptable birth control method. Females of non-childbearing potential must have undergone a sterilization procedure at least 6 months prior to the first dose * Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse during the trial and for 90 days after stopping the study medication and agree not to donate sperm during this time period Participants with ESRD on HD * Maintained on a stable regimen of HD within 3 months prior to first dosing Participants with Severe Renal Impairment * Estimated glomerular filtration rate (eGFR) at screening is \< 30 mL/min/1.73m\^2 Healthy Controls * Participant is within ± 10 years of the mean age and within 10% of the mean body mass index of severe renal impairment participants * eGFR at screening is \>=80 mL/min/1.73m\^2 Exclusion Criteria: All Participants * History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease whose current condition is considered unstable * History or presence of alcoholism and drug abuse within the past 6 months * Female participants who are pregnant or lactating * Regular user of any medication (including over the counter) that would significantly alter GFR * Donation of blood or significant blood loss within 56 days prior to the first dose of study medication(s) * Plasma donation within 7 days prior to the first dose of study medication(s) * A renal transplant or nephrectomy Participants with ESRD or Severe Renal Impairment * Rapidly fluctuating renal function

Outcomes

Primary Outcomes

Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Time frame: Up to 24 hours postdose

Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir

Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Time frame: 24 hours postdose

Maximum Plasma Concentration (Cmax) of Grazoprevir

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

Time frame: Up to 120 hours postdose

Time of Maximum Plasma Concentration (Tmax) of Grazoprevir

Time frame: Up to 120 hours postdose

Apparent Terminal Half-life (T1/2) of Grazoprevir

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10

Time frame: Up to 120 hours postdose

Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir

Data from ClinicalTrials.gov

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