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

NCT ID: NCT02089659

Last Updated: 2018-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-26
• Study Completion Date: 2014-05-12

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.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally

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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally

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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally

Interventions

Doravirine

Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally

Intervention Type: DRUG

Other Intervention Names

MK-1439

Eligibility Criteria

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Countries

United States

References

Khalilieh S, Yee KL, Liu R, Fan L, Sanchez RI, Auger P, Triantafyllou I, Stypinski D, Lasseter KC, Marbury T, Iwamoto M. Moderate Hepatic Impairment Does Not Affect Doravirine Pharmacokinetics. J Clin Pharmacol. 2017 Jun;57(6):777-783. doi: 10.1002/jcph.857. Epub 2016 Dec 27.

Reference Type: RESULT

PMID: 28026013 (View on PubMed)

Other Identifiers

MK-1439-019

Identifier Type: OTHER

Identifier Source: secondary_id

1439-019

Identifier Type: -

Identifier Source: org_study_id