A Study of Doravirine (MK-1439) in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439-005)

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.

Trial summary

This is a study to evaluate the safety, tolerability, pharmacokinetics, and antiretroviral activity of doravirine (MK-1439) as monotherapy in antiretroviral therapy (ART)-naïve, HIV-1-infected participants. Read more about this study

Who is it for?: Ages 18 to 55 years, men only
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?: Yes, some participants may receive a placebo
How many people: 18 participants
Where: No sites listed yet
Study dates: 21 Oct 2011to 10 Apr 2012
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 55 years
Men only
No healthy volunteers
Adult

Who may be able to join

Diagnosis of HIV-1-infection ≥3 months prior to screening
Participants with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
Body Mass Index (BMI) ≤35 kg/m^2
Other than HIV infection, participant's baseline health is judged to be stable
No clinically significant abnormality on electrocardiogram (ECG)
Participant is ART-naïve (defined as having never received any antiretroviral agent or ≤30 consecutive days of an investigational antiretroviral agent (excluding an Non-Nucleoside Reverse Transcriptase Inhibitor [NNRTI]) or ≤60 consecutive days of combination ART not including an NNRTI)
Participant is willing to receive no other ART for the duration of the treatment phase of this study.

Who cannot join

History of stroke, chronic seizures, or major neurological disorder
History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, or genitourinary abnormalities or diseases
History of clinically significant neoplastic disease
Participant has used any immune therapy agents or immunosuppressive therapy within 1 month prior to treatment in this study
Participant has one or more pre-existing risk factors for Torsades de Pointes (New York Heart Association Functional Classification II through IV heart failure, familial long-QT-syndrome, uncorrected hypokalemia, QTcF >470 msec)
Participant requires or is anticipated to require chronic daily prescription medications

Show all 17Show fewer

Current (active) diagnosis of acute hepatitis due to any cause
History of chronic Hepatitis C virus (HCV) unless there has been documented cure and/or patient with a positive serologic test for HCV has a negative HCV viral load.
Positive Hepatitis B surface antigen
Participant is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [Hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the post-study visit
Participant consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
Participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
Participant is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit
Participation in another investigational study within 4 weeks prior to the prestudy (screening) visit
History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
Current regular user (including use of any illicit drugs) or has a history of drug (including alcohol) abuse within approximately 1 year

About this study

Official title: A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-1439 in HIV-1 Infected Patients

Conditions: HIV-1 Infection
Being tested: Doravirine, Placebo

What participants receive

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

DoravirineDrug
Also called MK-1439
Doravirine tablets, orally, once daily for 7 days at a dose of 25 mg in Panel A and 200 mg in Panel B; dose in Panel C to be determined (≤200 mg).
PlaceboDrug
Placebo tablets once daily for 7 days.

Study groups in NCT01466985
Study group	Role	What they receive
Panel A: Doravirine 25 mg or Placebo	Experimental	Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days. Receives: Drug: Doravirine; Drug: Placebo
Panel B: Doravirine 200 mg or Placebo	Experimental	Panel B (doravirine 200 mg or placebo once daily for 7 days) will initiate upon satisfactory review of safety and tolerability from Panel A, and all safety, tolerability and pharmacokinetic data from the study MK-1439-001. Receives: Drug: Doravirine; Drug: Placebo
Panel C: Doravirine or Placebo	Experimental	Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels. Receives: Drug: Doravirine; Drug: Placebo

What is being measured

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

Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load
The change from baseline to Day 7 in plasma HIV RNA viral load was determined for each arm. Results are expressed as change in HIV RNA log10 copies/mL after 7 daily doses of doravirine or placebo. It was hypothesized that at least 1 dose of doravirine would be superior to placebo as documented by the upper bound of the 90% confidence interval <-1. Plasma HIV RNA levels were determined using the Abbott RealTime HIV assay which has a linear range from 40 to 10 million copies/mL.
Measured: Baseline and Day 7

Secondary outcomes (4)

Area Under the Plasma Concentration Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of Doravirine on Day 7
The AUC0-24hr of doravirine on Day 7 was determined in the doravirine treatment arms.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Maximum Plasma Concentration (Cmax) of Doravirine on Day 7
The Cmax of doravirine on Day 7 was determined in the doravirine treatment arms.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7
The C24hr of doravirine on Day 7 was determined in the doravirine treatment arms.
Measured: 24 hours postdose on Day 7 (Day 8)
Time to Maximum Plasma Concentration (Tmax) of Doravirine on Day 7
The Tmax of doravirine on Day 7 was determined in the doravirine treatment arms.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7

Timeline

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

21 Oct 201110 Apr 2012

First posted8 Nov 2011 (estimated)
Study start21 Oct 2011
Primary completion10 Apr 2012
Study completion10 Apr 2012

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: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01466985
Sponsor's protocol ID: 1439-005
Other IDs: 2011-003508-19, MK-1439-005
Status last verified: Sep 2018
First submitted: 4 Nov 2011
Last updated: 15 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Schurmann D, Sobotha C, Gilmartin J, Robberechts M, De Lepeleire I, Yee KL, Guo Y, Liu R, Wagner F, Wagner JA, Butterton JR, Anderson MS. A randomized, double-blind, placebo-controlled, short-term monotherapy study of doravirine in treatment-naive HIV-infected individuals. AIDS. 2016 Jan 2;30(1):57-63. doi: 10.1097/QAD.0000000000000876.
PubMed 26372481

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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All HIV-1 Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-1439 in HIV-1 Infected Patients
ClinicalTrials.gov ID: NCT01466985
Acronym / sponsor ID: 1439-005
Conditions: HIV-1 Infection
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 21 Oct 2011 (actual)
Primary completion: 10 Apr 2012 (actual)
Study completion: 10 Apr 2012 (actual)
First posted: 8 Nov 2011 (estimated)
Results: Posted 15 Feb 2019

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: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Panel A: Doravirine 25 mg or Placebo	Experimental	Drug: Doravirine, Drug: PlaceboParticipants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days.
Panel B: Doravirine 200 mg or Placebo	Experimental	Drug: Doravirine, Drug: PlaceboPanel B (doravirine 200 mg or placebo once daily for 7 days) will initiate upon satisfactory review of safety and tolerability from Panel A, and all safety, tolerability and pharmacokinetic data from the study MK-1439-001.
Panel C: Doravirine or Placebo	Experimental	Drug: Doravirine, Drug: PlaceboPanel C is optional. If conducted, the dose will be confirmed after review of data from prior panels.

Who may qualify

Ages: 18 to 55 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Diagnosis of HIV-1-infection ≥3 months prior to screening
Participants with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
Body Mass Index (BMI) ≤35 kg/m^2
Other than HIV infection, participant's baseline health is judged to be stable
No clinically significant abnormality on electrocardiogram (ECG)

Key exclusion criteria (17 listed)

History of stroke, chronic seizures, or major neurological disorder
History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, or genitourinary abnormalities or diseases
History of clinically significant neoplastic disease
Participant has used any immune therapy agents or immunosuppressive therapy within 1 month prior to treatment in this study
Participant has one or more pre-existing risk factors for Torsades de Pointes (New York Heart Association Functional Classification II through IV heart failure, familial long-QT-syndrome, uncorrected hypokalemia, QTcF >470 msec)

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-1439Doravirine tablets, orally, once daily for 7 days at a dose of 25 mg in Panel A and 200 mg in Panel B; dose in Panel C to be determined (≤200 mg).	Drug	Panel A: Doravirine 25 mg or Placebo, Panel B: Doravirine 200 mg or Placebo, Panel C: Doravirine or Placebo
PlaceboPlacebo tablets once daily for 7 days.	Drug	Panel A: Doravirine 25 mg or Placebo, Panel B: Doravirine 200 mg or Placebo, Panel C: Doravirine or Placebo

Primary outcome

Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load
Time frame: Baseline and Day 7
The change from baseline to Day 7 in plasma HIV RNA viral load was determined for each arm. Results are expressed as change in HIV RNA log10 copies/mL after 7 daily doses of doravirine or placebo. It was hypothesized that at least 1 dose of doravirine would be superior to placebo as documented by the upper bound of the 90% confidence interval <-1. Plasma HIV RNA levels were determined using the Abbott RealTime HIV assay which has a linear range from 40 to 10 million copies/mL.

4 secondary outcomes

Area Under the Plasma Concentration Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of Doravirine on Day 7
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Maximum Plasma Concentration (Cmax) of Doravirine on Day 7
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7
Time frame: 24 hours postdose on Day 7 (Day 8)
Time to Maximum Plasma Concentration (Tmax) of Doravirine on Day 7
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7

Results and safety

Results posted to the registry on 15 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Doravirine 25 mg	6	6
Doravirine 200 mg	6	6
Placebo	6	6

Primary outcome: Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load

Time frame: Baseline and Day 7. Least squares mean (95% Confidence Interval). Unit: Percentage change

Measure	Doravirine 25 mg n = 6	Doravirine 200 mg n = 6	Placebo n = 6
Value	-1.52 (-1.71 to -1.32)	-1.41 (-1.61 to -1.21)	-0.15 (-0.35 to 0.06)

Doravirine 25 mg vs Placebo: Least squares (LS) mean difference: -1.37 (90% CI -1.60 to -1.02), p <0.001, ANCOVA
Doravirine 200 mg vs Placebo: LS mean difference: -1.26 (90% CI -1.51 to -1.02), p <0.001, ANCOVA

Population analysed: All participants who received ≥1 dose of study drug are included (results are presented according to actual treatment received).

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 days after the last dose of study drug (up to 21 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Doravirine 25 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Doravirine 200 mg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Placebo	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Poststudy	1 of 18 (5.6%)	1 of 18 (5.6%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26372481Schurmann D, Sobotha C, Gilmartin J, Robberechts M, De Lepeleire I, Yee KL, Guo Y, Liu R, Wagner F, Wagner JA, Butterton JR, Anderson MS. A randomized, double-blind, placebo-controlled, short-term monotherapy study of doravirine in treatment-naive HIV-infected individuals. AIDS. 2016 Jan 2;30(1):57-63. doi: 10.1097/QAD.0000000000000876.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.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 7 inclusion and 17 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 15 Feb 2019. 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 15 Feb 2019). 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?

Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load (time frame: Baseline and Day 7). 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 NCT01466985, 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 15 Feb 2019.