NCT02089659

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

Completed Phase 1 Results posted Last updated 28 December 2018

What this trial tests

Phase 1 trial testing Doravirine in HIV-1 Infection in 16 participants. Completed in 12 May 2014.

Timeline

26 March 2014

Primary endpoint
12 May 2014

12 May 2014

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	16
Start date	26 March 2014
Primary completion	12 May 2014
Estimated completion	12 May 2014

Drugs / interventions tested

• Doravirine (DORAVIRINE) — full drug profile →

Conditions studied

• HIV-1 Infection — all drugs for HIV-1 Infection →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with HIV-1 Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Part 1: Participants With Moderate Hepatic Insufficiency	53.9	41.5 – 70.0
Part 1: Healthy Control Participants	54.6	42.1 – 71.0

Maximum Observed Plasma Concentration (Cmax) of Doravirine Primary · 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

Group	Value	95% CI
Part 1: Participants With Moderate Hepatic Insufficiency	1850	1420 – 2420
Part 1: Healthy Control Participants	2050	1570 – 2680

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

Group	Value	95% CI
Part 1: Participants With Moderate Hepatic Insufficiency	28.5	23.4 – 34.8
Part 1: Healthy Control Participants	30.6	25.1 – 37.3

Plasma Concentration of Doravirine at 24 Hours (C24) Primary · 24 hours postdose

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

Group	Value	95% CI
Part 1: Participants With Moderate Hepatic Insufficiency	842	658 – 1080
Part 1: Healthy Control Participants	847	662 – 1080

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 14 days after drug administration. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: Participants With Moderate Hepatic Insufficiency

Serious: 0/8 (0%)

Deaths: 0/8

Part 1: Healthy Control Participants

Serious: 0/8 (0%)

Deaths: 0/8

Other adverse events (6 terms — click to expand)

Reaction	System	Part 1: Participants With …	Part 1: Healthy Control Pa…
Headache	Nervous system disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Dizziness postural	Nervous system disorders	—	—
Somnolence	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT02089659 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Population Pharmacokinetics of Doravirine and Exposure-Response Analysis in Individuals with HIV-1.
   Yee KL, Ouerdani A, Claussen A, de Greef R, et al · · 2019 · cited 23× · PMID 30745394 · DOI 10.1128/aac.02502-18