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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 主要终点
- Number of Participants Experiencing Adverse Events (AEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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
研究组 & 干预措施
Pt 1: MK-3281 100 mg BID (Panel A)
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.
干预措施: MK-3281 (Drug)
Pt 1: MK-3281 200 mg BID (Panel B)
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.
干预措施: MK-3281 (Drug)
Pt 1: MK-3281 400 mg BID (Panel C)
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.
干预措施: MK-3281 (Drug)
Pt 1: MK-3281 800 mg BID (Panel D)
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.
干预措施: MK-3281 (Drug)
Pt 2: MK-3281 800 mg BID (Panel E)
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.
干预措施: MK-3281 (Drug)
Pt 2: MK-3281 800 mg BID (Panel F)
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.
干预措施: MK-3281 (Drug)
Pt 2: MK-3281 1200 mg BID (Panel G)
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.
干预措施: MK-3281 (Drug)
Placebo
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).
干预措施: Placebo to MK-3281 (Drug)
结局指标
主要结局
Number of Participants Experiencing Adverse Events (AEs)
时间窗: Up to 14 days after the last dose of study drug (up to 24 days maximum)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
Number of Participants Who Discontinued Study Medication Due to AEs
时间窗: Up to 14 days after the last dose of study drug (up to 24 days maximum)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
次要结局
- Maximum Plasma Concentration (Cmax) of MK-3281(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))
- 12-Hour Concentration of MK-3281 in Plasma (C12hr)(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))
- Apparent Half-Life (t ½) of MK-3281(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))
- Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281(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))
- AUC (0-12hr) Accumulation Ratio of MK-3281(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))
- Time To Reach Cmax (Tmax) of MK-3281(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))
- Cmax Accumulation Ratio of MK-3281(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))
- C12hr Accumulation Ratio of MK-3281(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))
- Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days(Baseline (pre-dose Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)