Hepatitis C, Chronic
Conditions
Brief summary
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.
Interventions
DRUGMK-8325
MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
DRUGPlacebo
Placebo to match MK-8325 capsules, orally, once per day for 5 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Outcome results
None listed