Trial Outcomes & Findings for A Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051) (NCT NCT02641067)

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

Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Results posted on

2019-02-08

Participant Flow

Participant milestones

Participant milestones
Measure	Severe Renal Impairment Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
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

A Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine	Total n=16 Participants Total of all reporting groups
Age, Customized 19 to 49 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized 50 to 59 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Age, Customized 60 to 69 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Body Weight	90.86 Kilogram STANDARD_DEVIATION 17.409 • n=5 Participants	90.93 Kilogram STANDARD_DEVIATION 6.086 • n=7 Participants	90.89 Kilogram STANDARD_DEVIATION 12.599 • n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine	64.5 μM•hr Interval 47.4 to 87.8	45.1 μM•hr Interval 33.2 to 61.4

PRIMARY outcome

Timeframe: 24 hours postdose

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Plasma Concentration of Doravirine at 24 Hours Postdose (C24)	943 nM Interval 710.0 to 1250.0	684 nM Interval 515.0 to 908.0

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Maximum Observed Plasma Concentration (Cmax) of Doravirine	1580 nM Interval 1210.0 to 2080.0	1900 nM Interval 1450.0 to 2500.0

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)	60.5 μM•hr Geometric Coefficient of Variation 56.3	41.0 μM•hr Geometric Coefficient of Variation 29.9

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Time to Maximum Observed Plasma Concentration (Tmax) of Doravirine	2.00 Hours Interval 0.5 to 4.0	1.50 Hours Interval 0.5 to 6.0

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Apparent Terminal Half-life (t1/2) of Plasma Doravirine	25.02 Hours Geometric Coefficient of Variation 36.4	16.69 Hours Geometric Coefficient of Variation 26.1

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Apparent Clearance of Plasma Doravirine After Extravascular Administration (CL/F)	3.53 Liter/hour Geometric Coefficient of Variation 63.9	5.38 Liter/hour Geometric Coefficient of Variation 32.8

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Population: All 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	Severe Renal Impairment n=8 Participants Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Controls n=8 Participants Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Apparent Volume of Distribution of Plasma Doravirine During the Terminal Phase (Vz/F)	127 Liters Geometric Coefficient of Variation 40.9	129 Liters Geometric Coefficient of Variation 28.3

Adverse Events

Severe Renal Impairment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Healthy Matched Control

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Severe Renal Impairment n=8 participants at risk Participants with severe renal impairment received a single oral dose of 100 mg doravirine	Healthy Matched Control n=8 participants at risk Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • Up to 14 days after drug administration The population analyzed consisted of 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 consisted of all participants who received at least 1 dose of study treatment.
Infections and infestations Conjunctivitis	12.5% 1/8 • Number of events 1 • Up to 14 days after drug administration The population analyzed consisted of 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 consisted of all participants who received at least 1 dose of study treatment.
Vascular disorders Phlebitis	0.00% 0/8 • Up to 14 days after drug administration The population analyzed consisted of 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 consisted of 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 Sponsor's policy on authorship is consistent with the requirements outlined in the ICH-Good Clinical Practice guidelines. In summary, authorship should reflect significant contribution to the design and conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript.
Publication restrictions are in place

Restriction type: OTHER