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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label Study to Investigate the Pharmacokinetics of MK-5172 and MK-8742 in Subjects With Renal Insufficiency

Conditions
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Chronic Hepatitis C, Renal Impairment

Intervention / Treatment
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* Drug: Grazoprevir
* Drug: Elbasvir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with End Stage Renal Disease on Hemodialysis<br>Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.. | Drug: Grazoprevir<br>* 100 mg oral tablet administered once a day for 10 days<br>Drug: Elbasvir<br>* 50 mg oral tablet administered once a day for 10 days<br>|
| Experimental: Participants with Severe Renal Impairment<br>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. | Drug: Grazoprevir<br>* 100 mg oral tablet administered once a day for 10 days<br>Drug: Elbasvir<br>* 50 mg oral tablet administered once a day for 10 days<br>|
| Experimental: Healthy Participants<br>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. | Drug: Grazoprevir<br>* 100 mg oral tablet administered once a day for 10 days<br>Drug: Elbasvir<br>* 50 mg oral tablet administered once a day for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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) | 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 | Up to 120 hours postdose | 
| Time of Maximum Plasma Concentration (Tmax) 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 | 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 | Up to 120 hours postdose | 
| Apparent Clearance After Extravascular Administration (CL/F) 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) | Up to 24 hours postdose | 
| Apparent Volume of Distribution After Extravascular Administration (Vz/F) 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 10 | Up to 24 hours postdose | 
| Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | 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) | Up to 24 hours postdose | 
| Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants) | 24 hours postdose | 
| Maximum Plasma Concentration (Cmax) of Elbasvir | 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 | Up to 120 hours postdose | 
| Time of Maximum Plasma Concentration (Tmax) of Elbasvir | 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 | Up to 120 hours postdose | 
| Apparent Terminal Half-life (T1/2) of Elbasvir | 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 | Up to 120 hours postdose | 
| Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | 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) | Up to 24 hours postdose | 
| Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir | 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 | Up to 24 hours postdose |