Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-3281 in Healthy and Hepatitis C Infected Male Participants (MK-3281-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: MK-3281; Drug: Placebo to MK-3281

Study type: Interventional

Funder types: Industry

Identifiers

NCT00635804

2008_507 (Other Identifier)

3281-002

2007-006245-40 (EudraCT Number)

Details and patient eligibility

About

This study will examine the safety, tolerability and plasma pharmacokinetics of multiple doses of MK-3281 in healthy male participants in Part I, and in Hepatitis C Virus (HCV)-infected male participants in Part II. The clinical efficacy of MK-3281, as measured by viral load reduction, will also be assessed in Part II. The primary hypothesis is that twice daily administration of MK-3281 for 10 days in healthy adult male participants and for 7 days in HCV-infected male participants is sufficiently safe and well tolerated, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.

The results of this study will guide dose selection for future studies in both healthy participants and HCV-infected participants.

Enrollment: 60 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participant is judged to be in good/stable health based on medical history, physical examination, vital signs, and laboratory safety tests performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
• Participant has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
• Participants with female partner(s) of childbearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
• Participant has a clinical diagnosis of chronic HCV infection (for Part II only).

Exclusion criteria

• Participant has a history of stroke, chronic seizures, or major neurological disorder
• Participant has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• Participant has a history of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment
• Participant has positive Hepatitis B surface antigen (or other evidence of active Hepatitis B infection) at the prescreening (study) visit
• For Healthy Panel (Part I), participant has evidence of chronic Hepatitis C virus infection at the prescreening (study) visit
• Participant has a history of documented Human Immunodeficiency Virus (HIV) infection

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 8 patient groups, including a placebo group

Pt 1: MK-3281 100 mg BID (Panel A)

Experimental group

Description:

Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.

Treatment:

Drug: MK-3281

Pt 1: MK-3281 200 mg BID (Panel B)

Experimental group

Description:

Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.

Treatment:

Drug: MK-3281

Pt 1: MK-3281 400 mg BID (Panel C)

Experimental group

Description:

Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.

Treatment:

Drug: MK-3281

Pt 1: MK-3281 800 mg BID (Panel D)

Experimental group

Description:

Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.

Treatment:

Drug: MK-3281

Pt 2: MK-3281 800 mg BID (Panel E)

Experimental group

Description:

Genotype (GT)1 HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.

Treatment:

Drug: MK-3281

Pt 2: MK-3281 800 mg BID (Panel F)

Experimental group

Description:

GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.

Treatment:

Drug: MK-3281

Pt 2: MK-3281 1200 mg BID (Panel G)

Experimental group

Description:

GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.

Treatment:

Drug: MK-3281

Placebo

Placebo Comparator group

Description:

Participants receive dose-matched placebo to MK-3281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).

Treatment:

Drug: Placebo to MK-3281