An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-8527 in Participants With Moderate and Severe Renal Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area Under the Concentration Versus Time Curve From Time 0 to Last Quantifiable Sample (AUC0-last) of MK-8527 in Plasma
研究概览
简要总结
The goal of this study is to evaluate the effect of moderate and severe renal impairment (RI) on the pharmacokinetics (PK), safety, and tolerability of MK-8527. There will be no hypothesis testing in the study.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Moderate and Severe RI
- •With the exception of RI, is in sufficient health for study participation.
- •Has stable renal function.
- •Matches mean age to participants with moderate and severe RI.
- •Has normal renal function.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •All participants
- •History of cancer (malignancy).
- •Positive test results for Human-immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV).
- •Had a major surgery or lost significant volume of blood within 56 days prior to dosing.
- •Donated plasma within 7 days prior to dosing.
- •Moderate and Severe RI
- •Failed renal transplant or had a nephrectomy.
- •End stage renal disease requiring dialysis.
- •Any significant arrhythmia or conduction abnormality.
- •Has non-sustained or sustained ventricular tachycardia.
研究组 & 干预措施
Moderate Renal Impairment
Participants with moderate renal impairment receive a single dose of MK-8527 on Day 1.
干预措施: MK-8527 (Drug)
Severe Renal Impairment
Participants with severe renal impairment receive a single dose of MK-8527 on Day 1.
干预措施: MK-8527 (Drug)
Healthy
Healthy participants receive a single dose of MK-8527 on Day 1.
干预措施: MK-8527 (Drug)
结局指标
主要结局
Area Under the Concentration Versus Time Curve From Time 0 to Last Quantifiable Sample (AUC0-last) of MK-8527 in Plasma
时间窗: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Blood samples were collected at pre-specified time points to determine the AUC0-last of MK-8527 in participant's plasma. AUC0 to last of MK-8527 was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration. AUC0-last was calculated using noncompartmental analysis.
Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of MK-8527 in Plasma
时间窗: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Blood samples were collected at pre-specified time points to determine the AUC0-inf of MK-8527 in participant's plasma. AUC0-inf was defined as AUC0-last + (Cest,last/λz) where Cest,last was the estimated last measurable concentration, and λz was the apparent first-order terminal elimination rate constant.
Maximum Concentration (Cmax) of MK-8527 in Plasma
时间窗: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Blood samples were collected at pre-specified time points to determine the Cmax of MK-8527 in participant's plasma. Cmax was defined as the maximum observed concentration of MK-8527 in plasma after the administration of a given dose.
Time to Maximum Concentration (Tmax) of MK-8527 in Plasma
时间窗: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Blood samples were collected at pre-specified time points to determine the tmax of MK-8527 in participant's plasma. Tmax of MK-8527 in plasma was determined by deriving the difference between the time of the blood draw associated with the Cmax and the time of study drug administration
Apparent Terminal Half-life (t1/2) of MK-8527 in Plasma
时间窗: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Blood samples were collected at pre-specified time points to determine the t1/2 of MK-8527 in participant's plasma. t1/2 was defined as 0.693/Apparent terminal elimination rate constant (λz).
Apparent Clearance (CL/F) of MK-8527 in Plasma
时间窗: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Blood samples were collected at pre-specified time points to determine the CL/F of MK-8527 in participant's plasma. CL/F was defined as dose/(AUC0-inf).
Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-8527 in Plasma
时间窗: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose
Blood samples were collected at pre-specified time points to determine the Vz/F of MK-8527 in participant's plasma. Vz/F of MK-8527 in plasma was determined using the formula Dose/(AUC0-inf × λz).
次要结局
- AUC0-inf of MK-8527-TP in PBMCs(Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose)
- Cmax of MK-8527-TP in PBMCs(Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose)
- Tmax of MK-8527-TP in PBMCs(Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 29 days)
- Number of Participants Who Discontinue Study Due to an AE(Up to approximately 29 days)
- AUC0-last of MK-8527-triphosphate (TP) in Peripheral Blood Mononuclear Cells (PBMCs)(Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose)
- Concentration at 168 Hours (C168) of MK-8527-TP in PBMCs(168 hours post dose)
- Concentration at 672 Hours (C672) of MK-8527-TP in PBMCs in Participants With Moderate and Severe Renal Impairment(672 hours post dose)
- C672 of MK-8527-TP in PBMCs in Healthy Participants(672 hours post dose)
- T1/2 of MK-8527-TP in PBMCs(Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose)