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

NCT02089659 | Completed Phase 1 Results

• 2 other identifiers: 1439-019MK-1439-019
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (3)

Part 1: Moderate Hepatic Insufficiency

EXPERIMENTAL

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

Part 1: Healthy Matched Control

EXPERIMENTAL

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

Drug: Doravirine

Part 2: Mild Hepatic Insufficiency

EXPERIMENTAL

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

Interventions

Doravirine DRUG

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

Also known as: MK-1439

Part 1: Healthy Matched Control; Part 1: Moderate Hepatic Insufficiency; Part 2: Mild Hepatic Insufficiency

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 28026013 RESULT

MeSH Terms

Interventions

doravirine

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: March 18, 2014
• Study Start: March 26, 2014
• Primary Completion: May 12, 2014
• Study Completion: May 12, 2014
• Last Updated: December 28, 2018
• Results First Posted: December 28, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share