An Open-Label Study to Investigate the Pharmacokinetics of MK-5172 and MK-8742 in Subjects With Renal Insufficiency
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir
研究概览
简要总结
Grazoprevir (MK-5172) and Elbasvir (MK-8742) were studied as the principal components of combination oral therapy for hepatitis C virus (HCV). The study examined the pharmacokinetic (PK) profiles of Grazoprevir and Elbasvir following 10 days of dosing in participants with end stage renal disease (ESRD) on hemodialysis (HD) or participants with severe renal impairment. Both groups were compared to healthy matched controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Participants
- •For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or be using an acceptable birth control method. Females of non-childbearing potential must have undergone a sterilization procedure at least 6 months prior to the first dose
- •Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse during the trial and for 90 days after stopping the study medication and agree not to donate sperm during this time period Participants with ESRD on HD
- •Maintained on a stable regimen of HD within 3 months prior to first dosing Participants with Severe Renal Impairment
- •Estimated glomerular filtration rate (eGFR) at screening is < 30 mL/min/1.73m^2 Healthy Controls
- •Participant is within ± 10 years of the mean age and within 10% of the mean body mass index of severe renal impairment participants
- •eGFR at screening is >=80 mL/min/1.73m^2
排除标准
- •All Participants
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease whose current condition is considered unstable
- •History or presence of alcoholism and drug abuse within the past 6 months
- •Female participants who are pregnant or lactating
- •Regular user of any medication (including over the counter) that would significantly alter GFR
- •Donation of blood or significant blood loss within 56 days prior to the first dose of study medication(s)
- •Plasma donation within 7 days prior to the first dose of study medication(s)
- •A renal transplant or nephrectomy Participants with ESRD or Severe Renal Impairment
- •Rapidly fluctuating renal function
研究组 & 干预措施
Participants with End Stage Renal Disease on Hemodialysis
Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days..
干预措施: Grazoprevir (Drug)
Participants with End Stage Renal Disease on Hemodialysis
Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days..
干预措施: Elbasvir (Drug)
Participants with Severe Renal Impairment
Participants with Severe Renal Impairment (estimated glomerular filtration rate <30 mL/min/1.73 m^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.
干预措施: Grazoprevir (Drug)
Participants with Severe Renal Impairment
Participants with Severe Renal Impairment (estimated glomerular filtration rate <30 mL/min/1.73 m^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.
干预措施: Elbasvir (Drug)
Healthy Participants
Healthy participants (estimated glomerular filtration rate >=80 mL/min/1.73 m^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.
干预措施: Grazoprevir (Drug)
Healthy Participants
Healthy participants (estimated glomerular filtration rate >=80 mL/min/1.73 m^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.
干预措施: Elbasvir (Drug)
结局指标
主要结局
Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir
时间窗: Up to 24 hours postdose
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Maximum Plasma Concentration (Cmax) of Grazoprevir
时间窗: Up to 120 hours postdose
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir
时间窗: Up to 24 hours postdose
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Apparent Terminal Half-life (T1/2) of Grazoprevir
时间窗: Up to 120 hours postdose
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10
Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir
时间窗: 24 hours postdose
Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir
时间窗: 24 hours postdose
Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir
时间窗: Up to 24 hours postdose
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time of Maximum Plasma Concentration (Tmax) of Elbasvir
时间窗: Up to 120 hours postdose
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir
时间窗: Up to 24 hours postdose
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir
时间窗: Up to 24 hours postdose
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time of Maximum Plasma Concentration (Tmax) of Grazoprevir
时间窗: Up to 120 hours postdose
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir
时间窗: Up to 24 hours postdose
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10
Maximum Plasma Concentration (Cmax) of Elbasvir
时间窗: Up to 120 hours postdose
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Apparent Terminal Half-life (T1/2) of Elbasvir
时间窗: Up to 120 hours postdose
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10
次要结局
未报告次要终点