A 2-Part, Open-Label, Singe-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-1439
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Doravirine
研究概览
简要总结
This study aimed to investigate the influence of hepatic insufficiency on the pharmacokinetics (PK) of doravirine (MK-1439). In Part 1, PK of doravirine in participants with moderate hepatic insufficiency was compared with that of healthy control subjects matched with regard to mean age and weight. If a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1, study Part 2 was to evaluate PK of doravirine in participants with mild hepatic insufficiency.
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
- •Body Mass Index (BMI) between 19 and 40 kg/m^2
- •Continuous non-smoker or moderate smoker of <20 cigarettes or equivalent per day. Agrees to consume <=10 cigarettes or equivalent per day from the time of screening through the period of sample collection.
- •In good health and with no clinically significant electrocardiogram abnormality
- •Hepatic impairment participants: diagnosis of chronic (>6 months), stable hepatic insufficiency with features of cirrhosis due to any etiology. Part 1 only: score of 7 to 9 on the Child-Pugh scale. Part 2: score of 5 to 6 on the Child-Pugh scale.
- •Females of childbearing potential: sexually inactive for >=14 days before study drug administration and throughout the study, or using 2 acceptable methods of barrier contraception from screening until 14 days after study drug administration.
排除标准
- •Mentally or legally incapacitated or has significant emotional problems at the time of screening or expected during the study
- •History or presence of clinically significant medical or psychiatric condition or disease
- •History or presence of drug abuse within the past 2 years
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds
- •Female participant who is pregnant or lactating
- •Positive results for breath alcohol or urine drug screen (unless due to prescription drug use and is approved by the investigator) at screening
- •Positive for HIV at screening
- •Unable to refrain from or anticipates the use of any drug known to be a significant inhibitor or inducer of cytochrome oxidase CYP3A or P-glycoprotein, or any medication or substance which cannot be discontinued at least 14 days before study drug administration and throughout the study.
- •Donation of >500 mL of blood or had significant blood loss within 56 days before study drug administration
- •Plasma donation within 7 days before study drug administration
- •Dosed in another clinical trial within 28 days before study drug administration
- •Healthy control participants only: positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) at screening;
研究组 & 干预措施
Part 1: Moderate Hepatic Insufficiency
Participants with moderate hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have moderate hepatic insufficiency based on the Child-Pugh scale.
干预措施: Doravirine (Drug)
Part 1: Healthy Matched Control
Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1.
干预措施: Doravirine (Drug)
Part 2: Mild Hepatic Insufficiency
Participants with mild hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have mild hepatic insufficiency based on the Child-Pugh scale. This arm was to be enrolled and investigated only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1.
干预措施: Doravirine (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Doravirine
时间窗: Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours postdose for all participants and at 96, 120, and 144 hours postdose for participants with hepatic insufficiency
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine
时间窗: Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours postdose for all participants and at 96, 120, and 144 hours postdose for participants with hepatic insufficiency
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine
时间窗: Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours postdose
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Plasma Concentration of Doravirine at 24 Hours (C24)
时间窗: 24 hours postdose
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
次要结局
未报告次要终点