Safety, Pharmacokinetics, and Pharmacodynamics of MK-6325 in Hepatitis C Virus (HCV) Infections (MK-6325-003)

Study Overview
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Brief Summary
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This is a 2 part study of the safety, pharmacokinetics and pharmacodynamics of MK-6325 in HCV-infected participants. Part I of the study will be for Genotype (GT) 1 HCV-infected participants who will be randomized to receive either MK-6325 or placebo. If the drug is shown to be safe and efficacious in Part I, Part II will enroll GT 3 HCV-infected participants who will be randomized to receive either MK-6325 or placebo.

Official Title
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A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-6325 in Hepatitis C Infected Male and Female Patients

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: MK-6325
* Drug: Placebo to MK-6325
* Drug: MK-6325
* Drug: Placebo to MK-6325
* Drug: MK-6325
* Drug: Placebo to MK-6325


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. Stable health No clinically significant abnormality on electrocardiogram (ECG) Clinical diagnosis of chronic HCV infection (G1 or G3) for at least 6 months and detectable HCV RNA in peripheral blood. Exclusion criteria: Pregnancy or intention to become pregnant or father a child during the course of the study. History of stroke, chronic seizures, major neurological disorder, or uncontrolled clinically significant psychiatric disorder (for example, depression). Estimated creatinine clearance of ≤70 mL/min. History of clinically significant endocrine, gastrointestinal (except HCV infection), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases whose current condition is considered clinically unstable. History of neoplastic disease other than adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix ≥10 years prior to the prestudy (screening) visit with no evidence of recurrence of likelihood of recurrence. Positive Hepatitis B surface antigen at the pre-study (screening) visit. History of documented HIV infection or positive HIV serology at the pre-study (screening) visit. Regular consumption of excessive amounts of alcohol, defined as greater than 2 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day. Excessive consumption, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) or coffee, tea, cola, or other caffeinated beverages per day. Major surgery, or donation or loss of 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the prestudy (screening) visit. History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food. Regular use of (including recreational use) of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 months. Exception: marijuana use is permitted at the discretion of the investigator and provided the participant can refrain from its use during the study. 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. Note: Participants with history of acute non-HCV-related hepatitis, which resolved >6 months before study can be enrolled. Previous treatment with other HCV protease inhibitors ≤3 months prior to the first dose of study drug. Previous exposure to interferon-alpha and/or ribavirin within 3 month prior to the first dose of MK-6325 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. Note: liver biopsy is not required for entry into the study.

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

Sexes Eligible for Study
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All

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: GT1-HCV 200 mg<br> | Drug: MK-6325<br>* Two 100 mg capsules, orally, once per day for 7 days<br>Drug: Placebo to MK-6325<br>* Two 100 mg capsules, orally, once per day for 7 days<br>|
| Experimental: GT1-HCV 400 mg<br> | Drug: MK-6325<br>* Four 100 mg capsules, orally, once per day for 7 days<br>Drug: Placebo to MK-6325<br>* Four 100 mg capsules, orally, once per day for 7 days<br>|
| Experimental: GTI-HCV 800 mg<br> | Drug: MK-6325<br>* Eight 100 mg capsules, orally, once per day for 7 days<br>Drug: Placebo to MK-6325<br>* Eight 100 mg capsules, orally, once per day for 7 days<br>|
| Experimental: GT3-HCV 200 mg<br> | Drug: MK-6325<br>* Two 100 mg capsules, orally, once per day for 7 days<br>Drug: Placebo to MK-6325<br>* Two 100 mg capsules, orally, once per day for 7 days<br>|
| Experimental: GT3-HCV 400 mg<br> | Drug: MK-6325<br>* Four 100 mg capsules, orally, once per day for 7 days<br>Drug: Placebo to MK-6325<br>* Four 100 mg capsules, orally, once per day for 7 days<br>|
| Experimental: GT3-HCV 800 mg<br> | Drug: MK-6325<br>* Eight 100 mg capsules, orally, once per day for 7 days<br>Drug: Placebo to MK-6325<br>* Eight 100 mg capsules, orally, once per 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 experiencing clinical and laboratory adverse events (AEs) (Parts I and II) |  | Up to 15 days after last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load reduction in GT1 HCV-infected participants (Part I) |  | 7 Days | 
| Viral load reduction in GT3 HCV-infected participants (Part II) |  | 7 Days |