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

Primary Purpose

HIV-1 Infection

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Doravirine

About this trial

This is an interventional treatment trial for HIV-1 Infection

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts 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;

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Part 1: Moderate Hepatic Insufficiency

Part 1: Healthy Matched Control

Part 2: Mild Hepatic Insufficiency

Arm 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.

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

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.

Outcomes

Primary Outcome Measures

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

Maximum Observed Plasma Concentration (Cmax) of Doravirine

Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02089659

First Posted

March 14, 2014

Last Updated

July 3, 2018

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02089659

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

March 26, 2014 (Actual)

Primary Completion Date

May 12, 2014 (Actual)

Study Completion Date

May 12, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV-1 Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Moderate Hepatic Insufficiency

Arm Type

Experimental

Arm Description

Arm Title

Part 1: Healthy Matched Control

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2: Mild Hepatic Insufficiency

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Doravirine

Other Intervention Name(s)

MK-1439

Intervention Description

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

Primary Outcome Measure Information:

Title

Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine

Description

Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method

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

Title

Maximum Observed Plasma Concentration (Cmax) of Doravirine

Description

Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method

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

Title

Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine

Description

Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method

Time Frame

Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours postdose

Title

Plasma Concentration of Doravirine at 24 Hours (C24)

Description

Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method

Time Frame

24 hours postdose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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;

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Citations:

PubMed Identifier

28026013

Citation

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.

Results Reference

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

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