Phase 1
N=16
A Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Doravirine (MK-1439) (MK-1439-019)
HIV-1 Infection
Bottom Line
View on ClinicalTrials.gov: NCT02089659 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Dec 2018
Primary outcome: Primary: Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine — 53.9; 54.6 µM*hr
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Doravirine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- May 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine |
53.9; 54.6 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Doravirine |
1850; 2050 | — |
| PRIMARY Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine |
28.5; 30.6 | — |
| PRIMARY Plasma Concentration of Doravirine at 24 Hours (C24) |
842; 847 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Body Mass Index (BMI) between 19 and 40 kg/m^2
- Continuous non-smoker or moderate smoker of 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;
Data sourced from ClinicalTrials.gov (NCT02089659). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.