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

Study Overview
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Brief Summary
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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.

Official Title
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A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Grazoprevir (MK-5172) in Hepatitis C Infected Male Patients

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Grazoprevir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 400 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 400 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 600 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 600 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 800 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 800 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 400 mg Grazoprevir - GT3<br>GT3 HCV-infected Participants: 400 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 600 mg Grazoprevir - GT3<br>GT3 HCV-infected Participants: 600 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 800 mg Grazoprevir - GT3<br>GT3 HCV-infected Participants: 800 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 200 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 200 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 100 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 100 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 50 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 50 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 200 mg Grazoprevir - GT3<br>GT3 HCV-infected Participants: 200 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 100 mg Grazoprevir - GT3<br>GT3 HCV-infected Participants: 100 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 50 mg Grazoprevir - GT3<br>GT3 HCV-infected Participants: 50 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 30 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 30 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|
| Experimental: 10 mg Grazoprevir - GT1<br>GT1 HCV-infected Participants: 10 mg Grazoprevir or Placebo | Drug: Grazoprevir<br>* 10, 30, 50, 100, 200, 400, 600 or 800 mg Grazoprevir tablets, orally, once a day for 7 days<br>Drug: Placebo<br>* Placebo tablet, orally, once a day for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical and Laboratory Adverse Events (AEs) | 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. | All AEs: 15 Days after last dose; Serious AEs (SAEs) up to 2 months after last dose (Up to 67 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve for 0 to 24 Hours Post-dose (AUC[0-24hr]) of Grazoprevir on Day 7 | 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. | Day 7 at the following time points: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose | 
| 24 Hour Plasma Concentration (C[24hr]) of Grazoprevir on Day 7 | 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. | Day 7 at 24 hours post-dose | 
| 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 | 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. | Baseline and up to approximately 2 months | 
| 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 | 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. | Baseline and up to approximately 2 months |