Clinical trial NCT00635804: Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-3281 in Healthy and Hepatitis C Infected Male Participants (MK-3281-002)
Official title: A 2-Part, Randomized, Double-Blind, Placebo-Controlled, Multiple-Rising Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-3281 in Healthy Male Subjects and Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-3281 in Hepatitis C Infected Male Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-03-14
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 14 days after the last dose of study drug (up to 24 days maximum)
measure: Number of Participants Who Discontinued Study Medication Due to AEs
timeFrame: Up to 14 days after the last dose of study drug (up to 24 days maximum)
Secondary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281
timeFrame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)
measure: Maximum Plasma Concentration (Cmax) of MK-3281
timeFrame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)
measure: 12-Hour Concentration of MK-3281 in Plasma (C12hr)
timeFrame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)
measure: Time To Reach Cmax (Tmax) of MK-3281
timeFrame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)
measure: Apparent Half-Life (t ½) of MK-3281
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose on Day 7 (HCV+ participants) or Day 10 (healthy participants)
measure: AUC (0-12hr) Accumulation Ratio of MK-3281
timeFrame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)
measure: Cmax Accumulation Ratio of MK-3281
timeFrame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)
measure: C12hr Accumulation Ratio of MK-3281
timeFrame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)
measure: Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days
timeFrame: Baseline (pre-dose Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: