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

NCT ID: NCT01937975

Last Updated: 2019-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-06
• Study Completion Date: 2013-12-17

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.

Conditions

Chronic Hepatitis C; Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants with End Stage Renal Disease on Hemodialysis

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

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

100 mg oral tablet administered once a day for 10 days

Elbasvir

Intervention Type: DRUG

50 mg oral tablet administered once a day for 10 days

Participants with Severe Renal Impairment

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.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

100 mg oral tablet administered once a day for 10 days

Elbasvir

Intervention Type: DRUG

50 mg oral tablet administered once a day for 10 days

Healthy Participants

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.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

100 mg oral tablet administered once a day for 10 days

Elbasvir

Intervention Type: DRUG

50 mg oral tablet administered once a day for 10 days

Interventions

Grazoprevir

100 mg oral tablet administered once a day for 10 days

Intervention Type: DRUG

Elbasvir

50 mg oral tablet administered once a day for 10 days

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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 Pharmacol. 2019 May;75(5):665-675. doi: 10.1007/s00228-018-2585-3. Epub 2019 Jan 25.

Reference Type: RESULT

PMID: 30680407 (View on PubMed)

Other Identifiers

5172-050

Identifier Type: -

Identifier Source: org_study_id