Safety, Pharmacokinetics, and Pharmacodynamics of MK-6325 in Hepatitis C Virus (HCV) Infections (MK-6325-003)

A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-6325 in Hepatitis C Infected Male and Female Patients

This is a 2 part study of the safety, pharmacokinetics and pharmacodynamics of MK-6325 in HCV-infected participants. Part I of the study will be for Genotype (GT) 1 HCV-infected participants who will be randomized to receive either MK-6325 or placebo. If the drug is shown to be safe and efficacious in Part I, Part II will enroll GT 3 HCV-infected participants who will be randomized to receive either MK-6325 or placebo.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: MK-6325; Drug: Placebo to MK-6325; Drug: MK-6325; Drug: Placebo to MK-6325; Drug: MK-6325; Drug: Placebo to MK-6325

• Study Type: Interventional
• Enrollment (Actual): 36
• 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:

• Body mass index (BMI) of 18 to ≤37 kg/m^2.
• Stable health
• No clinically significant abnormality on electrocardiogram (ECG)
• Clinical diagnosis of chronic HCV infection (G1 or G3) for at least 6 months and detectable HCV RNA in peripheral blood.

Exclusion criteria:

• Pregnancy or intention to become pregnant or father a child during the course of the study.
• History of stroke, chronic seizures, major neurological disorder, or uncontrolled clinically significant psychiatric disorder (for example, depression).
• Estimated creatinine clearance of ≤70 mL/min.
• History of clinically significant endocrine, gastrointestinal (except HCV infection), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases whose current condition is considered clinically unstable.
• History of neoplastic disease other than adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix ≥10 years prior to the prestudy (screening) visit with no evidence of recurrence of likelihood of recurrence.
• Positive Hepatitis B surface antigen at the pre-study (screening) visit.
• History of documented HIV infection or positive HIV serology at the pre-study (screening) visit.
• Regular 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.
• Excessive consumption, 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, or donation or loss of 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the prestudy (screening) visit.
• 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.
• Regular use of (including "recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 months. Exception: marijuana use is permitted at the discretion of the investigator and provided the participant can refrain from its use during the study.
• 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. Note: Participants with history of acute non-HCV-related hepatitis, which resolved >6 months before study can be enrolled.
• Previous treatment with other HCV protease inhibitors ≤3 months prior to the first dose of study drug.
• Previous exposure to interferon-alpha and/or ribavirin within 3 month prior to the first dose of MK-6325 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. Note: liver biopsy is not required for entry into the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GT1-HCV 200 mg	Drug: MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Eight 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Eight 100 mg capsules, orally, once per day for 7 days
Experimental: GT1-HCV 400 mg	Drug: MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Eight 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Eight 100 mg capsules, orally, once per day for 7 days
Experimental: GTI-HCV 800 mg	Drug: MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Eight 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Eight 100 mg capsules, orally, once per day for 7 days
Experimental: GT3-HCV 200 mg	Drug: MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Eight 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Eight 100 mg capsules, orally, once per day for 7 days
Experimental: GT3-HCV 400 mg	Drug: MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Eight 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Eight 100 mg capsules, orally, once per day for 7 days
Experimental: GT3-HCV 800 mg	Drug: MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Two 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Four 100 mg capsules, orally, once per day for 7 days; Drug: MK-6325; Eight 100 mg capsules, orally, once per day for 7 days; Drug: Placebo to MK-6325; Eight 100 mg capsules, orally, once per day for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants experiencing clinical and laboratory adverse events (AEs) (Parts I and II)	Up to 15 days after last dose of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Viral load reduction in GT1 HCV-infected participants (Part I)	7 Days
Viral load reduction in GT3 HCV-infected participants (Part II)	7 Days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: April 4, 2011
• First Submitted That Met QC Criteria: April 5, 2011
• First Posted (Estimate): April 6, 2011

Study Record Updates

• Last Update Posted (Estimate): February 5, 2015
• Last Update Submitted That Met QC Criteria: February 4, 2015
• Last Verified: February 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: 6325-003; 2010-023687-40 (EudraCT Number)