Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)
2015年6月5日 更新者：Merck Sharp & Dohme LLC
A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection
The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline.
It is anticipated that once-daily administration of a safe and well tolerated dose of MK-2248 will reduce VL by at least 3 log10 IU/mL.
研究概览
详细说明
In this Phase 1b study, the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of MK-2248 in HCV-infected participants will be evaluated as follows: Part I will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (A, B, C, and D).
Part II will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (E, F, G, and H).
Part III will assess sequentially ascending MK-2248 doses ranging up to ≤800 mg in 2 panels (I and J).
The potential relationship between plasma MK-2248 levels and VL reduction will be determined.
研究类型
介入性
注册 (实际的)
13
阶段
- 阶段1
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 65年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- clinical diagnosis of chronic HCV defined by positive serology for HCV or positive HCV RNA for at least 6 months and detectable HCV RNA in peripheral blood ≥10^5 IU/mL at screening
- Body Mass Index (BMI) ≥18 to <37 kg/m^2
- in good health other than HCV infection with normal laboratory values
Exclusion Criteria:
- history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- history of cancer other than adequately treated non-melanomatous skin carcinoma, malignancies which have been successfully treated ≥10 years prior with no recurrence, or cancer that is unlikely to sustain a recurrence for the duration of the trial
- history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
- positive for hepatitis B surface antigen or human immunodeficiency virus
- had major surgery or lost 1 unit of blood within 4 weeks prior to screening
- QTc interval ≥470 msec (males) or ≥480 msec (females)
- received prior treatment with other HCV inhibitors
- clinical or laboratory evidence of decompensated liver disease
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Part I: MK-2248 200 mg (Panel A)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part I: MK-2248 ≤800 mg (Panel B)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part I: MK-2248 ≤800 mg (Panel C)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part I: MK-2248 ≤800 mg (Panel D)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part II: MK-2248 200 mg (Panel E)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part II: MK-2248 ≤800 mg (Panel F)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part II: MK-2248 ≤800 mg (Panel G)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part II: MK-2248 ≤800 mg (Panel H)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part III: MK-2248 ≤800 mg (Panel I)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
实验性的：Part III: MK-2248 ≤800 mg (Panel J)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Maximum change from baseline in VL
大体时间：Up to Day 42
|
Up to Day 42
|
|
Number of participants experiencing an adverse event (AE)
大体时间：Up to Day 42
|
Up to Day 42
|
|
Number of participants who discontinue from study treatment due to an AE
大体时间：Up to Day 7
|
Up to Day 7
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)
大体时间：Up to Day 10
|
Up to Day 10
|
|
Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)
大体时间：Up to Day 10
|
Up to Day 10
|
|
Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)
大体时间：Up to Day 10
|
Up to Day 10
|
|
Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs
大体时间：Up to Day 10
|
Up to Day 10
|
|
Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma
大体时间：Up to Day 10
|
Up to Day 10
|
|
Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma
大体时间：Up to Day 10
|
Up to Day 10
|
|
Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma
大体时间：Up to Day 10
|
Up to Day 10
|
|
Apparent volume of distribution (V/F) of MK-2248 in plasma
大体时间：Up to Day 10
|
Up to Day 10
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2014年7月1日
初级完成 (实际的)
2014年11月1日
研究完成 (实际的)
2015年4月1日
研究注册日期
首次提交
2014年6月10日
首先提交符合 QC 标准的
2014年6月10日
首次发布 (估计)
2014年6月11日
研究记录更新
最后更新发布 (估计)
2015年6月8日
上次提交的符合 QC 标准的更新
2015年6月5日
最后验证
2015年6月1日
更多信息
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