A Dose-Ranging Study to Compare MK-1439 Plus TRUVADA® Versus Efavirenz Plus TRUVADA® in Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-1439-007 AM9)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
Part 1 - Dose-Ranging. Part 1 will evaluate the (1) safety and tolerability and (2) efficacy (antiretroviral activity) of 4 doses of 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 MK-1439 will be selected for further study after all participants complete the Week 24 visit in Part 1. Participants receiving any dose of MK-1439 in Part 1 will be switched to the selected MK-1439 dose and continue in the study for up to 96 weeks.
Part 2 - Selected Dose. Part 2 will be initiated after the MK-1439 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 MK-1439 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: MK-1439 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 |
- 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
- 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: | January 2016 |
| Estimated Primary Completion Date: | January 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: MK-1439 25 mg
MK-1439 25 mg + TRUVADA® Participants in this arm will receive MK-1439 25 mg in Part 1 and the selected MK-1439 dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz. |
Drug: MK-1439
Part 1: MK-1439 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching MK-1439 orally every morning with or without food for at least 24 weeks When the MK-1439 selected dose is determined after all participants reach Week 24, participants on other doses of MK-1439 will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of MK-1439 (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching MK-1439 orally every morning with or without food for 96 weeks 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 MK-1439 or placebo matching MK-1439 for 96 weeks
|
|
Experimental: MK-1439 50 mg
MK-1439 50 mg + TRUVADA® Participants in this arm will receive MK-1439 50 mg in Part 1 and the selected MK-1439 dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz. |
Drug: MK-1439
Part 1: MK-1439 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching MK-1439 orally every morning with or without food for at least 24 weeks When the MK-1439 selected dose is determined after all participants reach Week 24, participants on other doses of MK-1439 will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of MK-1439 (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching MK-1439 orally every morning with or without food for 96 weeks 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 MK-1439 or placebo matching MK-1439 for 96 weeks
|
|
Experimental: MK-1439 100 mg
MK-1439 100 mg + TRUVADA® Participants in this arm will receive MK-1439 100 mg in Part 1 and the selected MK-1439 dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz. |
Drug: MK-1439
Part 1: MK-1439 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching MK-1439 orally every morning with or without food for at least 24 weeks When the MK-1439 selected dose is determined after all participants reach Week 24, participants on other doses of MK-1439 will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of MK-1439 (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching MK-1439 orally every morning with or without food for 96 weeks 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 MK-1439 or placebo matching MK-1439 for 96 weeks
|
|
Experimental: MK-1439 200 mg
MK-1439 200 mg + TRUVADA® Participants in this arm will receive MK-1439 200 mg in Part 1 and the selected MK-1439 dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz. |
Drug: MK-1439
Part 1: MK-1439 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching MK-1439 orally every morning with or without food for at least 24 weeks When the MK-1439 selected dose is determined after all participants reach Week 24, participants on other doses of MK-1439 will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of MK-1439 (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching MK-1439 orally every morning with or without food for 96 weeks 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 MK-1439 or placebo matching MK-1439 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 MK-1439. |
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 MK-1439 or placebo matching MK-1439 for 96 weeks
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: Toll Free Number | 1-888-577-8839 |
Show 30 Study Locations More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT01632345 History of Changes |
| Other Study ID Numbers: | 1439-007, MK-1439-007 |
| Study First Received: | June 28, 2012 |
| Last Updated: | May 3, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immunologic Deficiency Syndromes Immune System Diseases |
Efavirenz Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents |
ClinicalTrials.gov processed this record on May 19, 2013