A Multiple Dose Study to Evaluate the Safety and Efficacy of MK-2748 in Hepatitis C-Infected Participants (MK-2748-002 AM1)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: Placebo; Drug: MK-2748

Study type: Interventional

Funder types: Industry

Identifiers

NCT01593735

2011-006296-18 (EudraCT Number)

2748-002

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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30 participants in 10 patient groups

Panel A: GT1, low dose

Experimental group

Description:

Participants with genotype 1 (GT1) Hepatitis C Virus (HCV) will receive low dose MK-2748 daily for 7 days.

Treatment:

Drug: Placebo

Drug: MK-2748

Panel B: GT1, lower dose

Experimental group

Description:

Participants with GT1 HCV will receive lower dose MK-2748 daily for 7 days.

Treatment:

Drug: Placebo

Drug: MK-2748

Panel C: GT1, dose based on Panels A+B

Experimental group

Description:

Participants with GT1 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels A (low dose) and B (lower dose).

Treatment:

Drug: Placebo

Drug: MK-2748

Panel G: GT1, dose based on Panels A+B+C

Experimental group

Description:

Participants with GT1 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels A (low dose), B (lower dose), and C.

Treatment:

Drug: Placebo

Drug: MK-2748

Panel H: GT1, dose based on Panels A+B+C+G

Experimental group

Description:

Participants with GT1 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels A (low dose), B (lower dose), C, and G.

Treatment:

Drug: Placebo

Drug: MK-2748

Panel D: GT3, low dose (Omitted)

Experimental group

Description:

Participants with genotype 3 (GT3) HCV were to receive low dose MK-2748 daily for 7 days. Panel D was omitted from the study design and participants were not enrolled in this panel.

Treatment:

Drug: Placebo

Drug: MK-2748

Panel E: GT3, high dose

Experimental group

Description:

Participants with genotype 3 (GT3) HCV will receive high dose MK-2748 daily for 7 days.

Treatment:

Drug: Placebo

Drug: MK-2748

Panel F: GT3, dose based on Panel E

Experimental group

Description:

Participants with GT3 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panel E (high dose).

Treatment:

Drug: Placebo

Drug: MK-2748

Panel I: GT3, dose based on Panels E+F

Experimental group

Description:

Participants with GT3 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels E (high dose) and F.

Treatment:

Drug: Placebo

Drug: MK-2748

Panel J: GT3, dose based on Panels E+F+I

Experimental group

Description:

Participants with GT3 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels E (high dose), F, and I.

Treatment:

Drug: Placebo

Drug: MK-2748