A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 主要终点
- Number of participants experiencing an adverse event (AE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Part I: MK-2248 200 mg (Panel A)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
Part II: MK-2248 200 mg (Panel E)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
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.
干预措施: MK-2248 (Drug)
结局指标
主要结局
Number of participants experiencing an adverse event (AE)
时间窗: Up to Day 42
Maximum change from baseline in VL
时间窗: Up to Day 42
Number of participants who discontinue from study treatment due to an AE
时间窗: Up to Day 7
次要结局
- Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)(Up to Day 10)
- Apparent volume of distribution (V/F) of MK-2248 in plasma(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(Up to Day 10)
- Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)(Up to Day 10)
- Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma(Up to Day 10)
- Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)(Up to Day 10)
- Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs(Up to Day 10)
- Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma(Up to Day 10)