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

Study Overview
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Brief Summary
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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.

Official Title
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A 2-Part, Open-Label, Singe-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-1439

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Doravirine


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Moderate Hepatic Insufficiency<br>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. | Drug: Doravirine<br>* Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally<br>* Other names: MK-1439;|
| Experimental: Part 1: Healthy Matched Control<br>Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. | Drug: Doravirine<br>* Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally<br>* Other names: MK-1439;|
| Experimental: Part 2: Mild Hepatic Insufficiency<br>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. | Drug: Doravirine<br>* Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally<br>* Other names: MK-1439;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | 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 | 
| Maximum Observed Plasma Concentration (Cmax) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | 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 | 
| Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours postdose | 
| Plasma Concentration of Doravirine at 24 Hours (C24) | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | 24 hours postdose |