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

HIV-1 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02089659
• Other study ID #: 1439-019
• Secondary ID: MK-1439-019
• Status: Completed
• Phase: Phase 1
• Start date: March 26, 2014
• Est. completion date: May 12, 2014

Study information

• Verified date: July 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: May 12, 2014
• Est. primary completion date: May 12, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Hepatic Insufficiency
• HIV-1 Infection
• Liver Failure

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & 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.8 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-8) 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
Primary	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
Primary	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
Primary	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