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Trial record 28 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

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

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ClinicalTrials.gov Identifier: NCT01937975
Recruitment Status : Completed
First Posted : September 10, 2013
Results First Posted : March 4, 2016
Last Update Posted : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 4, 2013
First Posted Date  ICMJE September 10, 2013
Results First Submitted Date  ICMJE February 3, 2016
Results First Posted Date  ICMJE March 4, 2016
Last Update Posted Date June 12, 2019
Actual Study Start Date  ICMJE September 6, 2013
Actual Primary Completion Date December 17, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir [ Time Frame: 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)
  • Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir [ Time Frame: 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)
  • Maximum Plasma Concentration (Cmax) of Grazoprevir [ Time Frame: 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
  • Time of Maximum Plasma Concentration (Tmax) of Grazoprevir [ Time Frame: 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 Terminal Half-life (T1/2) of Grazoprevir [ Time Frame: 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
  • Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir [ Time Frame: 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)
  • Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir [ Time Frame: 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
  • Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir [ Time Frame: 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)
  • Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir [ Time Frame: 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)
  • Maximum Plasma Concentration (Cmax) of Elbasvir [ Time Frame: 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
  • Time of Maximum Plasma Concentration (Tmax) of Elbasvir [ Time Frame: 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 [ Time Frame: 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
  • Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir [ Time Frame: 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 Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: September 4, 2013)
  • Area under the concentration-time curve from 0 to 24 hours postdose (AUC 0-24) of MK-5172 and MK-8742 [ Time Frame: 0 to 24 hours postdose ]
  • Plasma concentration at 24 hours postdose (C24) of MK-5172 and MK-8742 [ Time Frame: 24 hours postdose ]
  • Maximum plasma concentration (Cmax) of MK-5172 and MK-8742 [ Time Frame: 0 to 120 hours postdose ]
  • Time to maximum plasma concentration (Tmax) of MK-5172 and MK-8742 [ Time Frame: 0 to 120 hours postdose ]
  • Terminal phase half-life (T1/2) of MK-5172 and MK-8742 [ Time Frame: 0 to 120 hours postdose ]
  • Apparent clearance after extravascular administration (CL/F) of MK-5172 and MK-8742 [ Time Frame: 0 to 120 hours postdose ]
  • Apparent volume of distribution after extravascular administration (V/F) of MK-5172 and MK-8742 [ Time Frame: 0 to 120 hours postdose ]
Change History Complete list of historical versions of study NCT01937975 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050)
Official Title  ICMJE An Open-Label Study to Investigate the Pharmacokinetics of MK-5172 and MK-8742 in Subjects With Renal Insufficiency
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Hepatitis C
  • Renal Impairment
Intervention  ICMJE
  • Drug: Grazoprevir
    100 mg oral tablet administered once a day for 10 days
  • Drug: Elbasvir
    50 mg oral tablet administered once a day for 10 days
Study Arms  ICMJE
  • Experimental: 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..
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
  • Experimental: 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.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
  • Experimental: 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.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 4, 2013)
24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 17, 2013
Actual Primary Completion Date December 17, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT01937975
Other Study ID Numbers  ICMJE 5172-050
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP