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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: TRUVADA®; Drug: Placebo for Doravirine; Drug: Placebo for Efavirenz; Drug: Doravirine; Drug: Efavirenz

Study type: Interventional

Funder types: Industry

Identifiers

NCT01632345

2012-001573-93 (EudraCT Number)

1439-007

MK-1439-007 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 342 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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342 participants in 5 patient groups

Doravirine 25 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo for Doravirine

Drug: TRUVADA®

Drug: Doravirine

Doravirine 50 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo for Doravirine

Drug: TRUVADA®

Drug: Doravirine

Doravirine 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo for Doravirine

Drug: TRUVADA®

Drug: Doravirine

Doravirine 200 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo for Doravirine

Drug: TRUVADA®

Drug: Doravirine

Efavirenz

Active Comparator group

Description:

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

Treatment:

Drug: Placebo for Efavirenz

Drug: TRUVADA®

Drug: Efavirenz