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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV-1 Infection

Treatments: Drug: Doravirine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02089659

MK-1439-019 (Other Identifier)

1439-019

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 3 patient groups

Part 1: Moderate Hepatic Insufficiency

Experimental group

Description:

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.

Treatment:

Drug: Doravirine

Part 1: Healthy Matched Control

Experimental group

Description:

Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1.

Treatment:

Drug: Doravirine

Part 2: Mild Hepatic Insufficiency

Experimental group

Description:

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.

Treatment:

Drug: Doravirine