An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-8527 in Participants With Moderate and Severe Renal Impairment
概览
- 阶段
- 1 期
- 干预措施
- MK-8527
- 疾病 / 适应症
- Renal Impairment
- 发起方
- Merck Sharp & Dohme LLC
- 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
- 状态
- 已完成
- 最后更新
- 2个月前
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.
研究者
入排标准
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.
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
Severe Renal Impairment
Participants with severe renal impairment receive a single dose of MK-8527 on Day 1.
干预措施: MK-8527
Healthy
Healthy participants receive a single dose of MK-8527 on Day 1.
干预措施: MK-8527
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)