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

Primary Purpose

Chronic Hepatitis C, Renal Impairment

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Grazoprevir
Elbasvir
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Participants with End Stage Renal Disease on Hemodialysis

    Participants with Severe Renal Impairment

    Healthy Participants

    Arm Description

    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 (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 (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.

    Outcomes

    Primary Outcome Measures

    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)
    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)
    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
    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
    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
    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)
    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
    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)
    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)
    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
    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
    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
    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)
    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

    Secondary Outcome Measures

    Full Information

    First Posted
    September 4, 2013
    Last Updated
    June 11, 2019
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01937975
    Brief Title
    The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050)
    Official Title
    An Open-Label Study to Investigate the Pharmacokinetics of MK-5172 and MK-8742 in Subjects With Renal Insufficiency
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    September 6, 2013 (Actual)
    Primary Completion Date
    December 17, 2013 (Actual)
    Study Completion Date
    December 17, 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Hepatitis C, Renal Impairment

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    24 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Participants with End Stage Renal Disease on Hemodialysis
    Arm Type
    Experimental
    Arm Description
    Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days..
    Arm Title
    Participants with Severe Renal Impairment
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Healthy Participants
    Arm Type
    Experimental
    Arm 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.
    Intervention Type
    Drug
    Intervention Name(s)
    Grazoprevir
    Intervention Description
    100 mg oral tablet administered once a day for 10 days
    Intervention Type
    Drug
    Intervention Name(s)
    Elbasvir
    Intervention Description
    50 mg oral tablet administered once a day for 10 days
    Primary Outcome Measure Information:
    Title
    Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir
    Description
    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 Frame
    Up to 24 hours postdose
    Title
    Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir
    Description
    Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
    Time Frame
    24 hours postdose
    Title
    Maximum Plasma Concentration (Cmax) of Grazoprevir
    Description
    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
    Time Frame
    Up to 120 hours postdose
    Title
    Time of Maximum Plasma Concentration (Tmax) of Grazoprevir
    Description
    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
    Time Frame
    Up to 120 hours postdose
    Title
    Apparent Terminal Half-life (T1/2) of Grazoprevir
    Description
    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
    Time Frame
    Up to 120 hours postdose
    Title
    Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir
    Description
    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 Frame
    Up to 24 hours postdose
    Title
    Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir
    Description
    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
    Time Frame
    Up to 24 hours postdose
    Title
    Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir
    Description
    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)
    Time Frame
    Up to 24 hours postdose
    Title
    Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir
    Description
    Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
    Time Frame
    24 hours postdose
    Title
    Maximum Plasma Concentration (Cmax) of Elbasvir
    Description
    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
    Time Frame
    Up to 120 hours postdose
    Title
    Time of Maximum Plasma Concentration (Tmax) of Elbasvir
    Description
    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
    Time Frame
    Up to 120 hours postdose
    Title
    Apparent Terminal Half-life (T1/2) of Elbasvir
    Description
    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
    Time Frame
    Up to 120 hours postdose
    Title
    Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir
    Description
    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)
    Time Frame
    Up to 24 hours postdose
    Title
    Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir
    Description
    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
    Time Frame
    Up to 24 hours postdose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    30680407
    Citation
    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.
    Results Reference
    result

    Learn more about this trial

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

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