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

Chronic Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01937975
• Other study ID #: 5172-050
• Status: Completed
• Phase: Phase 1
• Start date: September 6, 2013
• Est. completion date: December 17, 2013

Study information

• Verified date: June 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 17, 2013
• Est. primary completion date: December 17, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Grazoprevir
100 mg oral tablet administered once a day for 10 days
• Elbasvir
50 mg oral tablet administered once a day for 10 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Caro L, Wenning L, Feng HP, Guo Z, Du L, Bhagunde P, Fandozzi C, Panebianco D, Marshall WL, Butterton JR, Iwamoto M, Yeh WW. Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment. Eur J Clin Pharm — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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