A Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Doravirine (MK-1439) (MK-1439-019)

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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.

Exclusion Criteria

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;

Arm && Interventions

Group	Intervention	Description
Part 2: Mild Hepatic Insufficiency	Doravirine	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.
Part 1: Moderate Hepatic Insufficiency	Doravirine	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.
Part 1: Healthy Matched Control	Doravirine	Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of Doravirine	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	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	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)	24 hours postdose	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method