An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of Islatravir (MK-8591) in Participants With Moderate Hepatic Impairment

Merck Sharp & Dohme LLC1 个研究点分布在 1 个国家目标入组 12 人开始时间: 2020年11月5日最近更新: 2025年7月17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: 12
试验地点: 1
主要终点: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma

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研究点记录与标识符相似试验

研究概览

简要总结

This is an open-label, single-dose study of the plasma pharmacokinetics (PK), safety, and tolerability of islatravir (ISL, MK-8591), and the intracellular PK of ISL triphosphate (ISL-TP) in male and female adult participants with moderate hepatic impairment and in healthy matched control 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 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•Healthy Control Participants:
•Is in good health based on medical history, physical examination, vital sign (VS) measurements and electrocardiograms (ECGs) performed prior to randomization
•Is in good health based on laboratory safety tests obtained at the screening visit and prior to administration of the initial dose of study drug.
•Has a body mass index (BMI) ≥18.5 and ≤40 kg/m2
•Hepatic Impairment Participants:
•Has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
•Has a score on the Child-Pugh scale ranging from 7 to 9 (moderate hepatic insufficiency) at screening
•With the exception of hepatic impairment, is in generally good health
•Has a BMI ≥ 18.5 and ≤ 40 kg/m2
•Healthy and Hepatic Impairment Participants:
•Males : uses contraception according to local regulations
•Females: is not pregnant or breastfeeding and one of the following applies:
•Is not a woman of childbearing potential (WOCBP) OR
•Is a WOCBP and uses an acceptable contraceptive method
•A WOCBP with negative highly sensitive pregnancy test within 24 hours of study intervention

排除标准

•Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
•Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years
•Has a history of cancer (malignancy)
•Has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or non-prescription drugs or food
•Has known hypersensitivity to the active substance or any of the excipients of the study drug
•Is positive for hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or HIV-2
•Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit
•Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to study drug administration, throughout the study, until the poststudy visit
•Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
•Has a QTc interval >470 for males or >480 ms for females, has a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), has uncorrected hypokalemia or hypomagnesemia, is taking concomitant medications that prolong the QT/QTc interval
•Is not considered low risk of having HIV infection
•Is a smoker or user of electronic cigarettes and/or has used nicotine or nicotine-containing products (eg, nicotine patch) within 3 months of screening
•Consumes greater than 3 glasses of alcoholic beverages per day
•Consumes more than 6 caffeinated beverages per day
•Is a regular user of illicit drugs or has a history of drug abuse within 2 years
•Presents any concern to the investigator regarding safe study participation
•Is unwilling to comply with study restrictions
•Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study

研究组 & 干预措施

Moderate Hepatic Impairment

Experimental

Participants receive a single dose of ISL 60 mg.

干预措施: Islatravir (Drug)

Healthy Controls

Experimental

Participants receive a single dose of ISL 60 mg.

干预措施: Islatravir (Drug)

结局指标

主要结局

Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma

时间窗: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma