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

A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2748 in Hepatitis C-Infected Participants

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: MK-2748; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: GT1, low dose; Participants with genotype 1 (GT1) Hepatitis C Virus (HCV) will receive low dose MK-2748 daily for 7 days.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel B: GT1, lower dose; Participants with GT1 HCV will receive lower dose MK-2748 daily for 7 days.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel C: GT1, dose based on Panels A+B; 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).	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel G: GT1, dose based on Panels A+B+C; 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.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel H: GT1, dose based on Panels A+B+C+G; 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.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel D: GT3, low dose (Omitted); 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.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel E: GT3, high dose; Participants with genotype 3 (GT3) HCV will receive high dose MK-2748 daily for 7 days.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel F: GT3, dose based on Panel E; 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).	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel I: GT3, dose based on Panels E+F; 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.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days
Experimental: Panel J: GT3, dose based on Panels E+F+I; 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.	Drug: MK-2748; MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment; Drug: Placebo; Placebo tablets, orally, once daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: May 4, 2012
• First Submitted That Met QC Criteria: May 4, 2012
• First Posted (Estimate): May 8, 2012

Study Record Updates

• Last Update Posted (Estimate): January 22, 2015
• Last Update Submitted That Met QC Criteria: January 21, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: 2748-002; 2011-006296-18 (EudraCT Number)