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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Renal Impairment; Chronic Hepatitis C

Treatments: Drug: Grazoprevir; Drug: Elbasvir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01937975

5172-050

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Participants with End Stage Renal Disease on Hemodialysis

Experimental group

Description:

Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days..

Treatment:

Drug: Elbasvir

Drug: Grazoprevir

Participants with Severe Renal Impairment

Experimental group

Description:

Participants with Severe Renal Impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.

Treatment:

Drug: Elbasvir

Drug: Grazoprevir

Healthy Participants

Experimental group

Description:

Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.

Treatment:

Drug: Elbasvir

Drug: Grazoprevir