A Two-Part, Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3682B (MK-3682/MK-5172/MK-8408 Fixed Dose Combination) When Administered to Subjects With Moderate and Severe Renal Insufficiency

Merck Sharp & Dohme LLC0 个研究点目标入组 16 人开始时间: 2016年1月19日最近更新: 2019年1月9日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Merck Sharp & Dohme LLC
入组人数: 16
主要终点: AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to compare the plasma pharmacokinetics (PK) of single doses of MK-3682B, a fixed dose combination (FDC) tablet containing uprifosbuvir (MK-3682) + grazoprevir (MK-5172) + ruzasvir (MK-8408) in participants with moderate (Part 1) and severe (Part 2) renal insufficiency (RI) to plasma PK in healthy participants.

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:
•Healthy adult males or females 18-80 years of age at screening
•Continuous non-smokers or moderate smokers (≤ 20 cigarettes/day or the equivalent) and agrees to consume no more than 10 cigarettes per day during the study period
•BMI ≥ 18 and ≤ 40.0 kg/m^2
•Agrees not to become pregnant or father a child during participation in the study
•Females of childbearing potential must either be abstinent for 14 days prior to dosing and throughout the study or be using an acceptable birth control method
•Vasectomized or non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after dosing
•Males must agree not to donate sperm from dosing until 90 days after dosing
•Moderate and Severe RI Participants:
•Baseline health is judged to be stable based on medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator
•Has had no clinically significant change in renal status at least 1 month prior to dosing and is not currently or has not previously been on hemodialysis
•Moderate RI: has baseline eGFR ≥ 30 mL/min/1.73m^2 and < 60 mL/min/1.73m^2, based on the Modification of Diet in Renal Disease (MDRD) equation at screening
•Severe RI: has baseline eGFR ≥ 15 mL/min/1.73m^2 and < 30 mL/min/1.73m^2, based on the MDRD equation at screening
•Healthy Participants:
•Is within ± 10 years of the mean age of moderate and severe RI arms
•BMI is within 10% of the mean BMI of participants with moderate and severe RI arms
•Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the Investigator
•Baseline CLcr ≥ 80 mL/min based on Cockcroft-Gault equation at screening

排除标准

•Is mentally or legally incapacitated or has significant emotional problems at the time of the screening
•History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator
•History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk by participating in the study
•Is female and pregnant or lactating
•Positive results for the urine or saliva drug screen or urine or breath alcohol screen at screening or check-in unless the positive drug screen is due to prescription drug use that is approved by the Investigator and Sponsor
•Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
•Seated heart rate is equal to or lower than 44 beats per minute (bpm) or higher than 100 bpm at screening
•Has had a renal transplant or has had nephrectomy
•Donation of blood or had significant blood loss within 56 days prior to dosing of study drug, or donation of plasma within 7 days prior to dosing
•Has participated in another clinical trial within 28 days prior to dosing of study drug

研究组 & 干预措施

Moderate RI Participants

Experimental

Participants with an estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73m^2 to <60 mL/min/1.73m^2 take 2 MK-3682B FDC tablets on Day 1 after fasting for 10 hours.

干预措施: MK-3682B (Drug)

Severe RI Participants

Experimental

Participants with an eGFR of ≥15 mL/min/1.73m^2 to <30 mL/min/1.73m^2 take 2 MK-3682B FDC tablets on Day 1 after fasting for 10 hours.

干预措施: MK-3682B (Drug)

Healthy Participants

Experimental

Healthy participants (creatinine clearance [CLcr] ≥80 mL/min) take 2 MK-362B FDC tablets on Day 1 after fasting for 10 hours. Healthy participants are matched to RI participants based on mean age, body mass index (BMI) and gender.

干预措施: MK-3682B (Drug)

结局指标

主要结局

AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir

时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose

AUC0-24 is a measure of total exposure to uprifosbuvir in plasma from dosing to 24 hours following oral administration of MK-3682B.

Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir

时间窗: 24 hours post-dose

C24 is the plasma concentration of uprifosbuvir 24 hours following oral administration of MK-3682B.

Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682)