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)

NCT ID: NCT01632345

Last Updated: 2019-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 342 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-12
• Study Completion Date: 2016-03-21

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Doravirine 25 mg

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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

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.

TRUVADA®

Intervention Type: 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 Doravirine

Intervention Type: DRUG

Placebo tablets matching doravirine

Doravirine 50 mg

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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

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.

TRUVADA®

Intervention Type: 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 Doravirine

Intervention Type: DRUG

Placebo tablets matching doravirine

Doravirine 100 mg

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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

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.

TRUVADA®

Intervention Type: 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 Doravirine

Intervention Type: DRUG

Placebo tablets matching doravirine

Doravirine 200 mg

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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

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.

TRUVADA®

Intervention Type: 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 Doravirine

Intervention Type: DRUG

Placebo tablets matching doravirine

Efavirenz

Efavirenz + TRUVADA® Participants in this arm will receive efavirenz in Part I and in Part II. These participants also receive placebo that matches doravirine.

Group Type: ACTIVE_COMPARATOR

Efavirenz

Intervention Type: DRUG

Efavirenz 600 mg tablet orally at bedtime taken without food on an empty stomach for 96 weeks

TRUVADA®

Intervention Type: 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 Efavirenz

Intervention Type: DRUG

Placebo tablets matching efavirenz

Interventions

Doravirine

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.

Intervention Type: DRUG

Efavirenz

Efavirenz 600 mg tablet orally at bedtime taken without food on an empty stomach for 96 weeks

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo for Doravirine

Placebo tablets matching doravirine

Intervention Type: DRUG

Placebo for Efavirenz

Placebo tablets matching efavirenz

Intervention Type: DRUG

Other Intervention Names

MK-1439

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 31355775 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31121013 (View on PubMed)

Other Identifiers

MK-1439-007

Identifier Type: OTHER

Identifier Source: secondary_id

2012-001573-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1439-007

Identifier Type: -

Identifier Source: org_study_id