Trial Outcomes & Findings for A Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Doravirine (MK-1439) (MK-1439-019) (NCT NCT02089659)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

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

Results posted on

2018-12-28

Participant Flow

Part 2 of the study was to enroll participants only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1. Because this was not observed, no participants were enrolled in Part 2 of the study.

Participant milestones

Participant milestones
Measure	Part 1: Participants With Moderate Hepatic Insufficiency Participants with moderate hepatic insufficiency received 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.	Part 1: Healthy Control Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1.
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Participants With Moderate Hepatic Insufficiency n=8 Participants Participants with moderate hepatic insufficiency received 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.	Part 1: Healthy Control Participants n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1.	Total n=16 Participants Total of all reporting groups
Age, Continuous	59 Years n=8 Participants	56 Years n=8 Participants	57 Years n=16 Participants
Sex: Female, Male Female	2 Participants n=8 Participants	2 Participants n=8 Participants	4 Participants n=16 Participants
Sex: Female, Male Male	6 Participants n=8 Participants	6 Participants n=8 Participants	12 Participants n=16 Participants
Child-Pugh Total Score Total Score = 7	2 Participants n=8 Participants • All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.	0 Participants All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.	2 Participants n=8 Participants • All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.
Child-Pugh Total Score Total Score = 8	4 Participants n=8 Participants • All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.	0 Participants All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.	4 Participants n=8 Participants • All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.
Child-Pugh Total Score Total Score = 9	2 Participants n=8 Participants • All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.	0 Participants All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.	2 Participants n=8 Participants • All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores.
Weight	82.0 kg n=8 Participants	79.8 kg n=8 Participants	80.9 kg n=16 Participants

PRIMARY outcome

Timeframe: 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

Population: The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model.

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

Outcome measures

Outcome measures
Measure	Part 1: Participants With Moderate Hepatic Insufficiency n=8 Participants Participants with moderate hepatic insufficiency received 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.	Part 1: Healthy Control Participants n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1.
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine	53.9 µM*hr Interval 41.5 to 70.0	54.6 µM*hr Interval 42.1 to 71.0

PRIMARY outcome

Timeframe: 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

Population: The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model.

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

Outcome measures

Outcome measures
Measure	Part 1: Participants With Moderate Hepatic Insufficiency n=8 Participants Participants with moderate hepatic insufficiency received 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.	Part 1: Healthy Control Participants n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1.
Maximum Observed Plasma Concentration (Cmax) of Doravirine	1850 nM Interval 1420.0 to 2420.0	2050 nM Interval 1570.0 to 2680.0

PRIMARY outcome

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

Population: The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model.

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

Outcome measures

Outcome measures
Measure	Part 1: Participants With Moderate Hepatic Insufficiency n=8 Participants Participants with moderate hepatic insufficiency received 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.	Part 1: Healthy Control Participants n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1.
Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine	28.5 µM*hr Interval 23.4 to 34.8	30.6 µM*hr Interval 25.1 to 37.3

PRIMARY outcome

Timeframe: 24 hours postdose

Population: The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model.

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

Outcome measures

Outcome measures
Measure	Part 1: Participants With Moderate Hepatic Insufficiency n=8 Participants Participants with moderate hepatic insufficiency received 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.	Part 1: Healthy Control Participants n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1.
Plasma Concentration of Doravirine at 24 Hours (C24)	842 nM Interval 658.0 to 1080.0	847 nM Interval 662.0 to 1080.0

Adverse Events

Part 1: Participants With Moderate Hepatic Insufficiency

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 1: Healthy Control Participants

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Part 1: Participants With Moderate Hepatic Insufficiency n=8 participants at risk Participants with moderate hepatic insufficiency received 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.	Part 1: Healthy Control Participants n=8 participants at risk Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1.
Gastrointestinal disorders Dry mouth	12.5% 1/8 • Number of events 1 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.	0.00% 0/8 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 1 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.	0.00% 0/8 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.	12.5% 1/8 • Number of events 1 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.
Nervous system disorders Dizziness postural	12.5% 1/8 • Number of events 1 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.	0.00% 0/8 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.
Nervous system disorders Headache	0.00% 0/8 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.	25.0% 2/8 • Number of events 2 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.
Nervous system disorders Somnolence	12.5% 1/8 • Number of events 1 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.	0.00% 0/8 • Up to 14 days after drug administration The population analyzed was all participants who received at least 1 dose of study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER