Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02089659
Recruitment Status : Completed
First Posted : March 18, 2014
Results First Posted : December 28, 2018
Last Update Posted : December 28, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: Doravirine Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 2-Part, Open-Label, Singe-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-1439
Actual Study Start Date : March 26, 2014
Actual Primary Completion Date : May 12, 2014
Actual Study Completion Date : May 12, 2014

Arm Intervention/treatment
Experimental: 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.
Drug: Doravirine
Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally
Other Name: MK-1439

Experimental: 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.
Drug: Doravirine
Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally
Other Name: MK-1439

Experimental: 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.
Drug: Doravirine
Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally
Other Name: MK-1439




Primary Outcome Measures :
  1. Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine [ Time Frame: 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

  2. Maximum Observed Plasma Concentration (Cmax) of Doravirine [ Time Frame: 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

  3. Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine [ Time Frame: 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

  4. Plasma Concentration of Doravirine at 24 Hours (C24) [ Time Frame: 24 hours postdose ]
    Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02089659


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
Publications of Results:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02089659    
Other Study ID Numbers: 1439-019
MK-1439-019 ( Other Identifier: Merck Protocol Number )
First Posted: March 18, 2014    Key Record Dates
Results First Posted: December 28, 2018
Last Update Posted: December 28, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatic Insufficiency
Liver Failure
Liver Diseases
Digestive System Diseases