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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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01632345
First received: June 28, 2012
Last updated: October 27, 2014
Last verified: October 2014
  Purpose

Part 1 - Dose-Ranging. Part 1 will evaluate the (1) safety and tolerability and (2) efficacy (antiretroviral activity) of 4 doses of doravirine (MK-1439) 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 1. Participants receiving any dose of doravirine in Part 1 will be switched to the selected doravirine dose and continue in the study for up to 96 weeks.

Part 2 - Selected Dose. Part 2 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 2 will evaluate the safety of the selected dose compared with efavirenz, particularly with regard to central nervous system adverse events (CNS events).

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


Condition Intervention Phase
HIV Infections
Drug: Doravirine
Drug: Efavirenz
Drug: TRUVADA®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants with HIV RNA <40 copies/mL [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and for Part 1 and Part 2 combined

  • Number of Participants with any Clinical or Laboratory Adverse Event [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]
    Analyzed for Part 1 and for Part 1 and Part 2 combined

  • Percentage of Participants with CNS Events [ Time Frame: 8 Weeks ] [ Designated as safety issue: Yes ]
    Analyzed for Part 1 and Part 2 combined

  • Percentage of Participants with CNS Events [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]
    Analyzed for Part 1 and Part 2 combined


Secondary Outcome Measures:
  • Percentage of Participants with HIV RNA <200 copies/mL [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and for Part 1 and Part 2 combined

  • Change from Baseline in Cluster of Differentiation 4 (CD4) Cell Counts [ Time Frame: Baseline and 24 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and for Part 1 and Part 2 combined

  • Percentage of Participants with HIV RNA <40 copies/mL [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and Part 2 combined

  • Number of Participants with any Clinical or Laboratory Adverse Event [ Time Frame: 48 Weeks ] [ Designated as safety issue: Yes ]
    Analyzed for Part 1 and Part 2 combined

  • Percentage of Participants with HIV RNA <200 copies/mL [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and Part 2 combined

  • Change from Baseline in CD4 Cell Counts [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and Part 2 combined

  • Percentage of Participants with HIV RNA <40 copies/mL [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and Part 2 combined

  • Number of Participants with any Clinical or Laboratory Adverse Event [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
    Analyzed for Part 1 and Part 2 combined

  • Percentage of Participants with HIV RNA <200 copies/mL [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and Part 2 combined

  • Change from Baseline in CD4 Cell Counts [ Time Frame: Baseline and 96 Weeks ] [ Designated as safety issue: No ]
    Analyzed for Part 1 and Part 2 combined


Estimated Enrollment: 320
Study Start Date: October 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doravirine 25 mg
doravirine 25 mg + TRUVADA® Participants in this arm will receive doravirine 25 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.
Drug: Doravirine
Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks
Drug: TRUVADA®
Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning alone or with doravirine or placebo matching doravirine for 96 weeks
Experimental: Doravirine 50 mg
Doravirine 50 mg + TRUVADA® Participants in this arm will receive doravirine 50 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.
Drug: Doravirine
Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks
Drug: TRUVADA®
Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning alone or with doravirine or placebo matching doravirine for 96 weeks
Experimental: Doravirine 100 mg
Doravirine 100 mg + TRUVADA® Participants in this arm will receive doravirine 100 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.
Drug: Doravirine
Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks
Drug: TRUVADA®
Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning alone or with doravirine or placebo matching doravirine for 96 weeks
Experimental: Doravirine 200 mg
Doravirine 200 mg + TRUVADA® Participants in this arm will receive doravirine 200 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.
Drug: Doravirine
Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks
Drug: TRUVADA®
Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning alone or with doravirine or placebo matching doravirine for 96 weeks
Active Comparator: Efavirenz
Efavirenz + TRUVADA® Participants in this arm will receive efavirenz in Part 1 and in Part 2. These participants also receive placebo that matches doravirine.
Drug: Efavirenz
Efavirenz 600 mg tablet or placebo matching efavirenz orally at bedtime taken without food on an empty stomach for 96 weeks
Drug: TRUVADA®
Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning alone or with doravirine or placebo matching doravirine for 96 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01632345     History of Changes
Other Study ID Numbers: 1439-007, MK-1439-007
Study First Received: June 28, 2012
Last Updated: October 27, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Efavirenz
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014