HIV InfectionsPhase 2NCT01632345

A Dose-Ranging Study to Compare Doravirine (MK-1439) Plus TRUVADA® Versus Efavirenz Plus TRUVADA® in Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-1439-007)

A Phase 2 study testing Doravirine, Efavirenz and TRUVADA® in people with HIV Infections, 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

The hypothesis tested in this study is that doravirine (MK-1439) at the final dose selected is superior to efavirenz, each given in combination with TRUVADA®, as measured by the percentage of participants with CNS events by Week 8. If superiority is established at Week 8, the same hypothesis will be tested for Week 24. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV Infections
What is being tested?: Doravirine, Efavirenz and TRUVADA®
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 342 participants
Where: No sites listed yet
Study dates: 12 Oct 2012to 21 Mar 2016
Phase: Phase 2
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

HIV-1 positive
No previous use of antiretroviral therapy (ART)
No signs of active pulmonary disease within 45 days before the start of study treatment
Clinically stable with no signs or symptoms of acute infection
No change in clinical status or chronic medications for at least 2 weeks before the start of study treatment
Participants of reproductive potential agree to remain abstinent in line with their preferred and usual lifestyle or use (or have their partner use) 2 acceptable methods of birth control throughout the study and for 12 weeks post study.
Participants not of reproductive potential, not sexually active, whose current partner(s) is not of reproductive potential, or whose sexual activity is exclusively homosexual are eligible without requiring the use of contraception.

Who cannot join

Males planning to impregnate or provide sperm donation for the duration of the study plus an additional 12 weeks. Females pregnant or breast-feeding or expecting to conceive or donate eggs for the duration of the study plus an additional 12 weeks.
Received any approved or experimental antiretroviral agents or is anticipated to receive such medications during the study.
Use of any immunomodulators or immunosuppressive therapy within one month before the study. Short courses of corticosteroids (e.g., for asthma exacerbation) are allowed.
Treatment for a viral infection other than HIV, such as hepatitis B, with an agent that is active against HIV
HIV resistance to emtricitabine, tenofovir disoproxil fumarate, and/or efavirenz.
History of renal or urinary obstructive disease or requires dialysis

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Active Hepatitis C virus (HCV) or Hepatitis B virus (HBV) co-infection
History of alcohol or other substance abuse
Participation in a study with an investigational compound/device within one month or is anticipating to participate in such a study during this study

About this study

Official title: Multicenter, Double-Blind, Randomized, 2-Part, Dose Ranging Study to Compare the Safety, and Antiretroviral Activity of MK-1439 Plus TRUVADA Versus Efavirenz Plus TRUVADA in Antiretroviral Treatment-Naive, HIV-1 Infected Patients

Read the detailed description

Part I - Dose-Ranging. Part I will evaluate the (1) safety and tolerability and (2) efficacy (antiretroviral activity) of 4 doses of doravirine compared with efavirenz, when each is given in combination with TRUVADA® for at least 24 weeks in approximately 200 participants. A single dose of doravirine will be selected for further study after all participants complete the Week 24 visit in Part I. Participants receiving any dose of doravirine in Part I will be switched to the selected doravirine dose and continue in the study for up to 96 weeks, but will not be randomized to Part II.

Part II - Selected Dose. Part II will be initiated after the doravirine dose has been selected as indicated above for Part 1. Approximately 120 additional participants will be randomized in 1:1 ratio to the selected dose of doravirine or efavirenz, each in combination with TRUVADA® for 96 weeks of blinded treatment. Part II will evaluate the safety of the selected dose compared with efavirenz, particularly with regard to central nervous system (CNS) adverse events.

Conditions: HIV Infections
Being tested: Doravirine, Efavirenz, TRUVADA®, Placebo for Doravirine, Placebo for Efavirenz
Medical subject headings: HIV Infections

What participants receive

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

DoravirineDrug
Also called MK-1439
Part I: Doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) depending upon randomization, taken orally every morning with or without food for at least 24 weeks. Part II: Selected dose of doravirine depending upon randomization (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet orally every morning with or without food for 96 weeks.
EfavirenzDrug
Efavirenz 600 mg tablet orally at bedtime taken without food on an empty stomach for 96 weeks
TRUVADA®Drug
Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning for 96 weeks
Placebo for DoravirineDrug
Placebo tablets matching doravirine
Placebo for EfavirenzDrug
Placebo tablets matching efavirenz

Study groups in NCT01632345
Study group	Role	What they receive
Doravirine 25 mg	Experimental	Doravirine 25 mg + TRUVADA® Participants in this arm will receive doravirine 25 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz. Receives: Drug: Doravirine; Drug: TRUVADA®; Drug: Placebo for Doravirine
Doravirine 50 mg	Experimental	Doravirine 50 mg + TRUVADA® Participants in this arm will receive doravirine 50 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz. Receives: Drug: Doravirine; Drug: TRUVADA®; Drug: Placebo for Doravirine
Doravirine 100 mg	Experimental	Doravirine 100 mg + TRUVADA® Participants in this arm will receive doravirine 100 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz. Receives: Drug: Doravirine; Drug: TRUVADA®; Drug: Placebo for Doravirine
Doravirine 200 mg	Experimental	Doravirine 200 mg + TRUVADA® Participants in this arm will receive doravirine 200 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz. Receives: Drug: Doravirine; Drug: TRUVADA®; Drug: Placebo for Doravirine
Efavirenz	Active comparator	Efavirenz + TRUVADA® Participants in this arm will receive efavirenz in Part I and in Part II. These participants also receive placebo that matches doravirine. Receives: Drug: Efavirenz; Drug: TRUVADA®; Drug: Placebo for Efavirenz

What is being measured

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

Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-24.
Measured: Up to Week 24
Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who discontinued therapy due to an AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group who discontinued therapy due to an AE was primarily assessed for Weeks 0-24.
Measured: Up to Week 24
Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was assessed for Weeks 0-24.
Measured: Up to Week 24
Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 8 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-8.
Measured: Up to Week 8
Percentage of Participants With CNS Events by Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 24 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-24.
Measured: Up to Week 24
Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the virologic response to doravirine at all studied doses (25 mg, 50 mg, 100 mg, and 200 mg), compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA <40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy.This primary outcome was analyzed for HIV-1 RNA <40 copies/mL in Part I.
Measured: Week 24
Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA <40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA <40 copies/mL in Part I \& Part II combined.
Measured: Week 24

Secondary outcomes (12)

Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA <40 copies/mL at Week 48. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA <40 copies/mL in Part I \& Part II combined.
Measured: Week 48
Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA <40 copies/mL at Week 96. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA <40 copies/mL in Part I \& Part II combined.
Measured: Week 96
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the virologic response to doravirine at all studied doses (25 mg, 50 mg, 100 mg, and 200 mg), compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA <200 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay.The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The NC=F approach was used as the primary approach to handle missing data for this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA <200 copies/mL in Part I.
Measured: Week 24
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA <200 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data for this analysis of efficacy. This secondary outcome was analyzed for HIV-1 RNA <200 copies/mL in Part I \& Part II combined.
Measured: Week 24
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Evaluation of the antiretroviral activity of doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA for 24 weeks, as measured by the percentage of participants with HIV-1 RNA <200 copies/mL at Week 48. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. This primary outcome was analyzed for RNA <200 copies/mL in Part I \& Part II combined.
Measured: Week 48
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA <200 copies/mL at Week 96. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-96. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA <200 copies/mL in Part I \& Part II combined.
Measured: Week 96
Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Evaluation of the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, and 200 mg), compared with participants receiving efavirenz 600 mg. The Observed Failure (OF) approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for participants who discontinued assigned treatment due to lack of efficacy.
Measured: Baseline, Week 24
Change From Baseline in CD4 Cell Count at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for participants who discontinued assigned treatment due to lack of efficacy.
Measured: Baseline, Week 24
Change From Baseline in CD4 Cell Count at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the change from baseline in the CD4 count at Week 48 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned treatment due to lack of efficacy.
Measured: Baseline, Week 48
Change From Baseline in CD4 Cell Count at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
A secondary endpoint in Part I/II combined was the change from baseline in the CD4 count at Week 96 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned treatment due to lack of efficacy.
Measured: Baseline, Week 96
Percentage of Participants With At Least 1 AE in Weeks 0-48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
A secondary outcome in Part I/II combined was the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 48 weeks of treatment. The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-48.
Measured: Up to Week 48
Percentage of Participants With At Least 1 AE in Weeks 0-96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
A secondary outcome in Part I/II combined was the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 96 weeks of treatment. The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-96.
Measured: Up to Week 96

Timeline

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

12 Oct 201221 Mar 2016

First posted2 Jul 2012 (estimated)
Study start12 Oct 2012
Primary completion3 Dec 2014
Study completion21 Mar 2016

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 (2)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 342 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01632345
Sponsor's protocol ID: 1439-007
Other IDs: MK-1439-007, 2012-001573-93
Status last verified: Jul 2019
First submitted: 28 Jun 2012
Last updated: 18 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Gatell JM, Morales-Ramirez JO, Hagins DP, Thompson M, Arasteh K, Hoffmann C, Raffi F, Osiyemi O, Dretler R, Harvey C, Xu X, Plettenberg A, Smith DE, Portilla J, Rugina S, Kumar S, Frobose C, Wan H, Rodgers A, Hwang C, Teppler H. Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial. Antivir Ther. 2019;24(6):425-435. doi: 10.3851/IMP3323.
PubMed 31355775
Thompson M, Orkin C, Molina JM, Sax P, Cahn P, Squires K, Xu X, Rodgers A, Kumar S, Teppler H, Martin E, Hanna G, Hwang C. Once-daily Doravirine for Initial Treatment of Adults Living With Human Immunodeficiency Virus-1: An Integrated Safety Analysis. Clin Infect Dis. 2020 Mar 17;70(7):1336-1343. doi: 10.1093/cid/ciz423.
PubMed 31121013

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 18 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multicenter, Double-Blind, Randomized, 2-Part, Dose Ranging Study to Compare the Safety, and Antiretroviral Activity of MK-1439 Plus TRUVADA Versus Efavirenz Plus TRUVADA in Antiretroviral Treatment-Naive, HIV-1 Infected Patients
ClinicalTrials.gov ID: NCT01632345
Acronym / sponsor ID: 1439-007
Conditions: HIV Infections
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 342 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 12 Oct 2012 (actual)
Primary completion: 3 Dec 2014 (actual)
Study completion: 21 Mar 2016 (actual)
First posted: 2 Jul 2012 (estimated)
Results: Posted 13 Dec 2017

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
Doravirine 25 mg	Experimental	Drug: Doravirine, Drug: TRUVADA®, Drug: Placebo for DoravirineDoravirine 25 mg + TRUVADA® Participants in this arm will receive doravirine 25 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.
Doravirine 50 mg	Experimental	Drug: Doravirine, Drug: TRUVADA®, Drug: Placebo for DoravirineDoravirine 50 mg + TRUVADA® Participants in this arm will receive doravirine 50 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.
Doravirine 100 mg	Experimental	Drug: Doravirine, Drug: TRUVADA®, Drug: Placebo for DoravirineDoravirine 100 mg + TRUVADA® Participants in this arm will receive doravirine 100 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.
Doravirine 200 mg	Experimental	Drug: Doravirine, Drug: TRUVADA®, Drug: Placebo for DoravirineDoravirine 200 mg + TRUVADA® Participants in this arm will receive doravirine 200 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.
Efavirenz	Active comparator	Drug: Efavirenz, Drug: TRUVADA®, Drug: Placebo for EfavirenzEfavirenz + TRUVADA® Participants in this arm will receive efavirenz in Part I and in Part II. These participants also receive placebo that matches doravirine.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

HIV-1 positive
No previous use of antiretroviral therapy (ART)
No signs of active pulmonary disease within 45 days before the start of study treatment
Clinically stable with no signs or symptoms of acute infection
No change in clinical status or chronic medications for at least 2 weeks before the start of study treatment

Key exclusion criteria (9 listed)

Males planning to impregnate or provide sperm donation for the duration of the study plus an additional 12 weeks. Females pregnant or breast-feeding or expecting to conceive or donate eggs for the duration of the study plus an additional 12 weeks.
Received any approved or experimental antiretroviral agents or is anticipated to receive such medications during the study.
Use of any immunomodulators or immunosuppressive therapy within one month before the study. Short courses of corticosteroids (e.g., for asthma exacerbation) are allowed.
Treatment for a viral infection other than HIV, such as hepatitis B, with an agent that is active against HIV
HIV resistance to emtricitabine, tenofovir disoproxil fumarate, and/or efavirenz.

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-1439Part I: Doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) depending upon randomization, taken orally every morning with or without food for at least 24 weeks. Part II: Selected dose of doravirine depending upon randomization (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet orally every morning with or without food for 96 weeks.	Drug	Doravirine 100 mg, Doravirine 200 mg, Doravirine 25 mg, Doravirine 50 mg
EfavirenzEfavirenz 600 mg tablet orally at bedtime taken without food on an empty stomach for 96 weeks	Drug	Efavirenz
TRUVADA®Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning for 96 weeks	Drug	Doravirine 100 mg, Doravirine 200 mg, Doravirine 25 mg, Doravirine 50 mg, Efavirenz
Placebo for DoravirinePlacebo tablets matching doravirine	Drug	Doravirine 100 mg, Doravirine 200 mg, Doravirine 25 mg, Doravirine 50 mg
Placebo for EfavirenzPlacebo tablets matching efavirenz	Drug	Efavirenz

Primary outcome

Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Time frame: Up to Week 24
Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-24.
Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Time frame: Up to Week 24
Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who discontinued therapy due to an AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group who discontinued therapy due to an AE was primarily assessed for Weeks 0-24.
Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Up to Week 24
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was assessed for Weeks 0-24.
Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Up to Week 8
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 8 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-8.
Percentage of Participants With CNS Events by Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Up to Week 24
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 24 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-24.
Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Time frame: Week 24
Assessment of the virologic response to doravirine at all studied doses (25 mg, 50 mg, 100 mg, and 200 mg), compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA <40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy.This primary outcome was analyzed for HIV-1 RNA <40 copies/mL in Part I.
Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Week 24
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA <40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA <40 copies/mL in Part I \& Part II combined.

12 secondary outcomes

Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Week 48
Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Week 96
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Time frame: Week 24
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Week 24
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Week 48
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Week 96
Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Time frame: Baseline, Week 24
Change From Baseline in CD4 Cell Count at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Baseline, Week 24
Change From Baseline in CD4 Cell Count at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Baseline, Week 48
Change From Baseline in CD4 Cell Count at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Baseline, Week 96
Percentage of Participants With At Least 1 AE in Weeks 0-48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Up to Week 48
Percentage of Participants With At Least 1 AE in Weeks 0-96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Time frame: Up to Week 96

Results and safety

Results posted to the registry on 13 Dec 2017, 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 I: Doravirine 25 mg	41	41
Part I: Doravirine 50 mg	43	43
Part I: Doravirine 100 mg	42	42
Part I: Doravirine 200 mg	41	41
Part I: Efavirenz 600 mg	43	43
Part II: Doravirine 100 mg	66	66
Part II: Efavirenz 600 mg	66	66

Primary outcome: Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)

Time frame: Up to Week 24. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Doravirine 25 mg: Part I n = 40	Doravirine 50 mg: Part I n = 43	Doravirine 100 mg : Part I n = 42	Doravirine 200 mg: Part I n = 41	Efavirenz 600 mg: Part I n = 42
Value	90.0 (76.3 to 97.2)	93.0 (80.9 to 98.5)	71.4 (55.4 to 84.3)	85.4 (70.8 to 94.4)	83.3 (68.6 to 93.0)

Doravirine 25 mg: Part I vs Efavirenz 600 mg: Part I: Difference (Doravirine - Efavirenz): 6.7 (95% CI -9.0 to 22.4)
Doravirine 50 mg: Part I vs Efavirenz 600 mg: Part I: Difference (Doravirine - Efavirenz): 9.7 (95% CI -4.6 to 24.9)
Doravirine 100 mg : Part I vs Efavirenz 600 mg: Part I: Difference (Doravirine - Efavirenz): -11.9 (95% CI -27.9 to 6.3)

Population analysed: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in Part I.

Primary outcome: Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)

Time frame: Up to Week 24. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Doravirine 25 mg: Part I n = 40	Doravirine 50 mg: Part I n = 43	Doravirine 100 mg: Part I n = 42	Doravirine 200 mg: Part I n = 41	Efavirenz 600 mg: Part I n = 42
Value	2.5 (0.1 to 13.2)	7.0 (1.5 to 19.1)	2.4 (0.1 to 12.6)	0.0 (0.0 to 8.6)	4.8 (0.6 to 16.2)

Doravirine 25 mg: Part I vs Efavirenz 600 mg: Part I: Difference (Doravirine - Efavirenz): -2.3 (95% CI -13.7 to 8.8)
Doravirine 50 mg: Part I vs Efavirenz 600 mg: Part I: Difference (Doravirine - Efavirenz): 2.2 (95% CI -9.9 to 14.7)
Doravirine 100 mg: Part I vs Efavirenz 600 mg: Part I: Difference (Doravirine - Efavirenz): -2.4 (95% CI -13.8 to 8.2)

Population analysed: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in Part I.

Primary outcome: Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)

Time frame: Up to Week 24. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Doravirine 100 mg: Part I/II (Combined) n = 108	Efavirenz 600 mg: Part I/II (Combined) n = 108
Value	75.0 (65.7 to 82.8)	85.2 (77.1 to 91.3)

Doravirine 100 mg: Part I/II (Combined) vs Efavirenz 600 mg: Part I/II (Combined): Difference: -10.2 (95% CI -20.9 to 0.5)

Population analysed: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in either Part I or Part II.

Primary outcome: Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)

Time frame: Up to Week 8. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Doravirine 100 mg: Part I/II (Combined) n = 108	Efavirenz 600 mg: Part I/II (Combined) n = 108
Value	24.1 (16.4 to 33.3)	44.4 (34.9 to 54.3)

Doravirine 100 mg: Part I/II (Combined) vs Efavirenz 600 mg: Part I/II (Combined): Difference (Doravirine - Efavirenz): -20.4 (95% CI -32.4 to -7.8), p = 0.002, Miettinen and Nurminen method

Population analysed: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in either Part I or Part II.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: 96 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Doravirine 25 mg (n=40)	4 of 40 (10%)	31 of 40 (77.5%)	Not reported
Doravirine 50 mg (n=43)	1 of 43 (2.3%)	35 of 43 (81.4%)	Not reported
Doravirine 100 mg (n=108)	11 of 108 (10.2%)	78 of 108 (72.2%)	Not reported
Doravirine 200 mg (n=41)	3 of 41 (7.3%)	36 of 41 (87.8%)	Not reported
Efavirenz 600 mg: Part I (n=108)	13 of 108 (12%)	82 of 108 (75.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31355775Gatell JM, Morales-Ramirez JO, Hagins DP, Thompson M, Arasteh K, Hoffmann C, Raffi F, Osiyemi O, Dretler R, Harvey C, Xu X, Plettenberg A, Smith DE, Portilla J, Rugina S, Kumar S, Frobose C, Wan H, Rodgers A, Hwang C, Teppler H. Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial. Antivir Ther. 2019;24(6):425-435. doi: 10.3851/IMP3323.
Derived from this study: PubMed 31121013Thompson M, Orkin C, Molina JM, Sax P, Cahn P, Squires K, Xu X, Rodgers A, Kumar S, Teppler H, Martin E, Hanna G, Hwang C. Once-daily Doravirine for Initial Treatment of Adults Living With Human Immunodeficiency Virus-1: An Integrated Safety Analysis. Clin Infect Dis. 2020 Mar 17;70(7):1336-1343. doi: 10.1093/cid/ciz423.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/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 2 study testing Doravirine, Efavirenz and TRUVADA® in people with HIV Infections, 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 9 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 18 Jul 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 13 Dec 2017). 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 of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) (time frame: Up to Week 24). The study lists 7 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 NCT01632345, which also lists 2 linked publications.

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 18 Jul 2019; AzTrials last refreshed its copy on 2 Nov 2026.