A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C-Infected Males (MK-8325-002)

Study Overview
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Brief Summary
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This study is being done to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of MK-8325 in male hepatitis C virus (HCV)-infected participants. There will be 3 parts to this study. Part I will enroll only genotype 1 (GT1) HCV patients, Part II will enroll only genotype 3 (GT3) HCV-infected participants, and Part III will enroll only GT1a HCV-infected participants. All parts may run concurrently, or may be staggered as needed by the clinical sites.

Official Title
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A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C Infected Males

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: MK-8325
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Body mass index (BMI) of 18 to ≤37 kg/m^2 Diagnosis of chronic HCV infection Must be infected with HCV GT1a, GT1b, or GT3 Exclusion criteria: Co-infection with GT1 and GT3 HCV History of stroke, chronic seizures, or major neurological disorder History of clinically significant endocrine, gastrointestinal (excepting HCV infection), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases History of neoplastic disease Positive Hepatitis B surface antigen History of human immunodeficiency virus (HIV) infection or positive HIV serology Major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior History of significant multiple and/or severe allergies (including latex allergy), or anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food Current regular user (including recreational use) of any illicit drugs or history of drug (including alcohol) abuse within approximately 2 months Evidence or history of chronic hepatitis not caused by HCV including but not limited to non-HCV viral hepatitis, non-alcoholic steatohepatitis (NASH), drug-induced hepatitis, autoimmune hepatitis Previous treatments(s) with nonstructural 5A (NS5A) protein inhibitors Treatment with protease inhibitor(s) <30 days prior to study enrollment Previous exposure to interferon-alpha and/or ribavirin within 3 months prior to the first dose of MK-8325 in the study Clinical or laboratory evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score ≥3) from prior liver biopsy

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: Panel A (GT1 10 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel B (GT1 50 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel C (GT1 100 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel D (GT1 200 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel E (GT3 10 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel F (GT3 50 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel G (GT3 100 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel H (GT3 200 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel I (GT1a 10 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Experimental: Panel J (GT1a 50 mg)<br> | Drug: MK-8325<br>* MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)<br>|
| Placebo Comparator: Placebo Panel<br> | Drug: Placebo<br>* Placebo to match MK-8325 capsules, orally, once per day for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Day 5 in plasma HCV ribonucleic acid (RNA) in GT1 participants |  | Day 1 predose and 2, 4, 8, 12, 24 and 36 hours post-dose, Days 3 and 4 predose, Day 5 predose and 2, 4, 8, 12, and 24 hours post-dose. | 
| Mean maximum reduction from baseline through Day 5 in HCV ribonucleic acid (RNA) in GT3 participants |  | Day 1 predose and 2, 4, 8, 12, 24 and 36 hours post-dose, Days 3 and 4 predose, Day 5 predose and 2, 4, 8, 12, and 24 hours post-dose. | 
| Number of participants experiencing at least one adverse event |  | Day 1 up to 56 days | 
| Number of participants discontinuing study drug due to an adverse event |  | Days 1-5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough plasma concentration (C24hr) of MK-8325 |  | Day 1 predose and 0.25 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose and Day 5 predose and 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16, 24, 36,48, 72, 96, 120, 144, 168, 192, 216, and 240 hours post-dose | 
| Area under the concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-8325 |  | Day 1 predose and 0.25 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose and Day 5 predose and 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose | 
| Maximum plasma concentration (Cmax) of MK-8325 |  | Day 1 predose and 0.25 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose and Day 5 predose and 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16, 24, 36,48, 72, 96, 120, 144, 168, 192, 216, and 240 hours post-dose |