HIV-1 InfectionPhase 1NCT02089659

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

A Phase 1 study testing Doravirine in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: HIV-1 Infection
What is being tested?: Doravirine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: No sites listed yet
Study dates: 26 Mar 2014to 12 May 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 12Show fewer

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;

About this study

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

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.

Conditions: HIV-1 Infection
Being tested: Doravirine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DoravirineDrug
Also called MK-1439
Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally

Study groups in NCT02089659
Study group	Role	What they receive
Part 1: Moderate Hepatic Insufficiency	Experimental	Participants with moderate hepatic insufficiency receive 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. Receives: Drug: Doravirine
Part 1: Healthy Matched Control	Experimental	Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. Receives: Drug: Doravirine
Part 2: Mild Hepatic Insufficiency	Experimental	Participants with mild hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have mild hepatic insufficiency based on the Child-Pugh scale. This arm was to be enrolled and investigated only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1. Receives: Drug: Doravirine

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Measured: 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
Maximum Observed Plasma Concentration (Cmax) of Doravirine
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Measured: 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
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
Measured: Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours postdose
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
Measured: 24 hours postdose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Mar 201412 May 2014

First posted18 Mar 2014 (estimated)
Study start26 Mar 2014
Primary completion12 May 2014
Study completion12 May 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02089659
Sponsor's protocol ID: 1439-019
Other IDs: MK-1439-019
Status last verified: Jul 2018
First submitted: 14 Mar 2014
Last updated: 28 Dec 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf

Publications

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.857. Epub 2016 Dec 27.
PubMed 28026013

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 28 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 2-Part, Open-Label, Singe-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-1439
ClinicalTrials.gov ID: NCT02089659
Acronym / sponsor ID: 1439-019
Conditions: HIV-1 Infection
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 26 Mar 2014 (actual)
Primary completion: 12 May 2014 (actual)
Study completion: 12 May 2014 (actual)
First posted: 18 Mar 2014 (estimated)
Results: Posted 28 Dec 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Part 1: Moderate Hepatic Insufficiency	Experimental	Drug: DoravirineParticipants with moderate hepatic insufficiency receive 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 Matched Control	Experimental	Drug: DoravirineHealthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1.
Part 2: Mild Hepatic Insufficiency	Experimental	Drug: DoravirineParticipants with mild hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have mild hepatic insufficiency based on the Child-Pugh scale. This arm was to be enrolled and investigated only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DoravirineAlso: MK-1439Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally	Drug	Part 1: Healthy Matched Control, Part 1: Moderate Hepatic Insufficiency, Part 2: Mild Hepatic Insufficiency

Primary outcome

Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine
Time frame: 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
Maximum Observed Plasma Concentration (Cmax) of Doravirine
Time frame: 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
Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine
Time frame: 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
Plasma Concentration of Doravirine at 24 Hours (C24)
Time frame: 24 hours postdose
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method

Results and safety

Results posted to the registry on 28 Dec 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Participants With Moderate Hepatic Insufficiency	8	8
Part 1: Healthy Control Participants	8	8
Part 2: Participants With Mild Hepatic Insufficiency	0	0

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

Time frame: 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. Geometric mean (95% Confidence Interval). Unit: µM*hr

Measure	Part 1: Participants With Moderate Hepatic Insufficiency n = 8	Part 1: Healthy Control Participants n = 8
Value	53.9 (41.5 to 70.0)	54.6 (42.1 to 71.0)

Part 1: Participants With Moderate Hepatic Insufficiency vs Part 1: Healthy Control Participants: Geometric Mean Ratio: 0.99 (90% CI 0.72 to 1.35)

Population analysed: 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.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Doravirine

Measure	Part 1: Participants With Moderate Hepatic Insufficiency n = 8	Part 1: Healthy Control Participants n = 8
Value	1850 (1420 to 2420)	2050 (1570 to 2680)

Part 1: Participants With Moderate Hepatic Insufficiency vs Part 1: Healthy Control Participants: Geometric Mean Ratio: 0.90 (90% CI 0.66 to 1.24)

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

Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours postdose. Geometric mean (95% Confidence Interval). Unit: µM*hr

Measure	Part 1: Participants With Moderate Hepatic Insufficiency n = 8	Part 1: Healthy Control Participants n = 8
Value	28.5 (23.4 to 34.8)	30.6 (25.1 to 37.3)

Part 1: Participants With Moderate Hepatic Insufficiency vs Part 1: Healthy Control Participants: Geometric Mean Ratio: 0.93 (90% CI 0.74 to 1.18)

Primary outcome: Plasma Concentration of Doravirine at 24 Hours (C24)

Time frame: 24 hours postdose. Geometric mean (95% Confidence Interval). Unit: nM

Measure	Part 1: Participants With Moderate Hepatic Insufficiency n = 8	Part 1: Healthy Control Participants n = 8
Value	842 (658 to 1080)	847 (662 to 1080)

Part 1: Participants With Moderate Hepatic Insufficiency vs Part 1: Healthy Control Participants: Geometric Mean Ratio: 0.99 (90% CI 0.74 to 1.33)

Adverse events

Time frame: Up to 14 days after drug administration. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Participants With Moderate Hepatic Insufficiency	0 of 8 (0%)	4 of 8 (50%)	0 of 8
Part 1: Healthy Control Participants	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28026013Khalilieh 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.857. Epub 2016 Dec 27.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Doravirine in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02089659, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2018.