A Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Male Participants (MK-5172-004)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00998985
First received: October 20, 2009
Last updated: February 3, 2016
Last verified: January 2016
  Purpose
This multiple dose study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of grazoprevir (MK-5172) in Genotype (GT) 1 and GT3 Hepatitis C virus (HCV)- infected participants. The primary hypothesis is that administration of grazoprevir for 7 days is sufficiently safe and well tolerated in HCV-infected males.

Condition Intervention Phase
Hepatitis C
Drug: Grazoprevir
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Grazoprevir (MK-5172) in Hepatitis C Infected Male Patients

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants With Clinical and Laboratory Adverse Events (AEs) [ Time Frame: All AEs: 15 Days after last dose; Serious AEs (SAEs) up to 2 months after last dose (Up to 67 days) ] [ Designated as safety issue: Yes ]
    An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.


Secondary Outcome Measures:
  • Area Under the Curve for 0 to 24 Hours Post-dose (AUC[0-24hr]) of Grazoprevir on Day 7 [ Time Frame: Day 7 at the following time points: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose ] [ Designated as safety issue: No ]
    Blood samples were collected on Day 7 at pre-dose up to 24 hours post-dose in order to determine the AUC 0-24hrs of Grazoprevir. It is hypothesized that the Geometric Mean of Day 7 Grazoprevir AUC0-24hr. exceeds 3.2 uM.hr.

  • 24 Hour Plasma Concentration (C[24hr]) of Grazoprevir on Day 7 [ Time Frame: Day 7 at 24 hours post-dose ] [ Designated as safety issue: No ]
    Blood samples were collected on Day 7 at 24 hours post-dose in order to determine the C24hr of Grazoprevir. It is hypothesized that the Geometric Mean of Day 7 Grazoprevir C24hr exceeds 28 nM.

  • Maximum log10 HCV RNA Reduction From Baseline Following Administration of Grazoprevir in Participants With GT1 HCV or Pooled GT1 and GT3 HCV Participants Treated With Placebo [ Time Frame: Baseline and up to approximately 2 months ] [ Designated as safety issue: No ]
    Blood samples were collected at baseline and at intervals up to 2 months post-dose in order to determine the maximum log10 reduction from baseline in plasma HCV RNA, expressed in international units (IU)/mL.

  • Maximum log10 HCV RNA Reduction From Baseline Following Administration of Grazoprevir in Participants With GT3 HCV or Pooled GT1 and GT3 HCV Participants Treated With Placebo [ Time Frame: Baseline and up to approximately 2 months ] [ Designated as safety issue: No ]
    Blood samples were collected at baseline and at intervals up to 2 months post-dose in order to determine the maximum log10 reduction from baseline in plasma HCV RNA.


Enrollment: 91
Study Start Date: February 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 400 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 400 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 600 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 600 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 800 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 800 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 400 mg Grazoprevir - GT3
GT3 HCV-infected Participants: 400 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 600 mg Grazoprevir - GT3
GT3 HCV-infected Participants: 600 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 800 mg Grazoprevir - GT3
GT3 HCV-infected Participants: 800 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 200 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 200 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 100 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 100 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 50 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 50 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 200 mg Grazoprevir - GT3
GT3 HCV-infected Participants: 200 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 100 mg Grazoprevir - GT3
GT3 HCV-infected Participants: 100 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 50 mg Grazoprevir - GT3
GT3 HCV-infected Participants: 50 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 30 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 30 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days
Experimental: 10 mg Grazoprevir - GT1
GT1 HCV-infected Participants: 10 mg Grazoprevir or Placebo
Drug: Grazoprevir
10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days
Drug: Placebo
Placebo tablet, orally, once a day for 7 days

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Baseline health is stable.
  • Has a clinical diagnosis of chronic HCV infection.

Exclusion Criteria:

  • Has a history of stroke or chronic seizures.
  • Has a history of cancer.
  • Has a history of human immunodeficiency virus (HIV) infection.
  • Has had major surgery, donated blood or participated in another investigational study within the past 3 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00998985

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00998985     History of Changes
Other Study ID Numbers: 5172-004  2009_678  2009-015563-13 
Study First Received: October 20, 2009
Results First Received: February 3, 2016
Last Updated: February 3, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on April 27, 2016