Hepatitis C
Conditions
Brief summary
This is a multiple dose study of the safety and efficacy of MK-2748 to be done in 2 Parts. Part I will enroll genotype 1 (GT1) hepatitis C virus (HCV)-infected participants and Part II will enroll genotype 3 (GT3) HCV-infected participants. Both Parts may run concurrently or may be staggered.
Interventions
DRUGMK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment
DRUGPlacebo
Placebo tablets, orally, once daily for 7 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of chronic HCV infection (GT1 or GT3) for at least 6 months and detectable HCV-RNA in peripheral blood * Body mass index (BMI) of 18 to 37 kg/m\^2 * No clinically significant abnormality on electrocardiogram (ECG) * Stable health * Willing to use appropriate contraception throughout the study and for 90 days after last dose of study drug
Exclusion criteria
* Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study * History of stroke, chronic seizures, or major neurological disorder * History of clinically significant endocrine, gastrointestinal (excepting HCV infection), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases * History of neoplastic disease (exceptions of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or other malignancies which have been successfully treated ≥10 years prior and unlikely to recur * Positive Hepatitis B surface antigen * Documented human immunodeficiency virus (HIV) infection * 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 * Consumption of excessive amounts, 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, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to study enrollment * 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 * Current regular user (including recreational use) of any illicit drugs or history of drug (including alcohol) abuse within approximately 2 months prior to enrollment * 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 treatment with other HCV NS3/4A protease inhibitors * Previous exposure to interferon-alpha and/or ribavirin within 3 months prior to study enrollment * Clinical or laboratory evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score ≥3) * Participation in another investigational study within 4 weeks prior to enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in HCV RNA viral load (log 10 copies/mL) in GT1 HCV-infected participants | Predose on Day 1 through Day 56 |
| Change from baseline in HCV RNA viral load (log 10 copies/mL) in GT3 HCV-infected participants | Predose on Day 1 through Day 56 |
| Number of participants experiencing clinical or laboratory adverse events (AEs) | From first dose up to 21 days |
| Number of participants discontinued from study treatment due to AEs | From Day 1 through Day 7 |
Secondary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-2748 | Day 1 and Day 7, predose through 24 hours post-dose |
| Plasma concentration of MK-2748 (C24) on Day 7 of dosing | 24 hours post-dose on Day 7 |
Outcome results
None listed