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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: MK-6325; Drug: Placebo to MK-6325

Study type: Interventional

Funder types: Industry

Identifiers

NCT01329913

6325-003

2010-023687-40 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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36 participants in 6 patient groups

GT1-HCV 200 mg

Experimental group

Treatment:

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

GT1-HCV 400 mg

Experimental group

Treatment:

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

GTI-HCV 800 mg

Experimental group

Treatment:

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

GT3-HCV 200 mg

Experimental group

Treatment:

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

GT3-HCV 400 mg

Experimental group

Treatment:

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

GT3-HCV 800 mg

Experimental group

Treatment:

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325

Drug: Placebo to MK-6325

Drug: Placebo to MK-6325

Drug: MK-6325