The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050)
- Conditions
- Renal ImpairmentChronic Hepatitis C
- Interventions
- Registration Number
- NCT01937975
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Participants with End Stage Renal Disease on Hemodialysis Grazoprevir Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.. Participants with Severe Renal Impairment Elbasvir 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. Participants with End Stage Renal Disease on Hemodialysis Elbasvir Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.. Healthy Participants Elbasvir 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. Participants with Severe Renal Impairment Grazoprevir 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. Healthy Participants Grazoprevir 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.
- Primary Outcome Measures
Name Time Method Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir Up to 24 hours postdose Blood for determination of Elbasvir 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)
Maximum Plasma Concentration (Cmax) of Grazoprevir Up to 120 hours postdose 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
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir Up to 24 hours postdose Blood for determination of Elbasvir 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)
Apparent Terminal Half-life (T1/2) of Grazoprevir Up to 120 hours postdose 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
Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir 24 hours postdose Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir 24 hours postdose Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir Up to 24 hours postdose 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 of Maximum Plasma Concentration (Tmax) of Elbasvir Up to 120 hours postdose Blood for determination of Elbasvir 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
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir Up to 24 hours postdose Blood for determination of Elbasvir 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 10
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir Up to 24 hours postdose 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 of Maximum Plasma Concentration (Tmax) of Grazoprevir Up to 120 hours postdose 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
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir Up to 24 hours postdose 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 10
Maximum Plasma Concentration (Cmax) of Elbasvir Up to 120 hours postdose Blood for determination of Elbasvir 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
Apparent Terminal Half-life (T1/2) of Elbasvir Up to 120 hours postdose Blood for determination of Elbasvir 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
- Secondary Outcome Measures
Name Time Method