Clinical trial NCT01593735: A Multiple Dose Study to Evaluate the Safety and Efficacy of MK-2748 in Hepatitis C-Infected Participants (MK-2748-002 AM1)
Official title: A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2748 in Hepatitis C-Infected Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-05-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in HCV RNA viral load (log 10 copies/mL) in GT1 HCV-infected participants
timeFrame: Predose on Day 1 through Day 56
measure: Change from baseline in HCV RNA viral load (log 10 copies/mL) in GT3 HCV-infected participants
timeFrame: Predose on Day 1 through Day 56
measure: Number of participants experiencing clinical or laboratory adverse events (AEs)
timeFrame: From first dose up to 21 days
measure: Number of participants discontinued from study treatment due to AEs
timeFrame: From Day 1 through Day 7
Secondary outcomes:
measure: Area under the plasma concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-2748
timeFrame: Day 1 and Day 7, predose through 24 hours post-dose
measure: Plasma concentration of MK-2748 (C24) on Day 7 of dosing
timeFrame: 24 hours post-dose on Day 7
Other outcomes:
Locations:
Study officials:
References: