TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.

NCT ID: NCT00540449

Last Updated: 2016-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 694 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2011-12-31

Brief Summary

The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a fixed background regimen consisting of emtricitabine (FTC) + tenofovir disoproxil fumarate (TDF), in HIV-1 infected patients who have not yet taken any anti-HIV drugs. The following evaluations will be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution, relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics, medical resource utilization and treatment adherence.

Detailed Description

Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced sequentially for use in the clinic. Currently, patients are routinely being treated with 3 or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This is a Phase III, randomized (study medication is assigned by chance), double-blind (neither the study physician nor the patient knows the name of the study assigned medication), double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up period. Patients will be randomly assigned to TMC278 or to efavirenz, either of these treatments will be in combination with two other anti-HIV drugs (2 NRTIs: emtricitabine (FTC) + tenofovir (TDF)). TDF/FTC will be administered as a fixed dose combination if available. The hypothesis to be provided in this study is that the investigational drug TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e., suppressing of the plasma viral load to a level < 50 HIV-1 RNA (ribonucleic acid) copies/mL) in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by physical examination, interview to assess health and well being, and laboratory testing on blood and urine samples. Experimental Group: One tablet of TMC278 25 mg once daily plus one tablet of placebo once daily that looks just like efavirenz (EFV) plus tenofovir/emtricitabine; Control Group: One tablet of Placebo once daily that looks just like TMC278 plus EFV 600 mg once daily plus tenofovir/emtricitabine.

Conditions

HIV Infections; HIV-1; Human Immunodeficiency Virus Type 1

Study Design

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

Study Groups

Efavirenz

Efavirenz 600mg once daily for 96 weeks

Group Type: ACTIVE_COMPARATOR

Efavirenz

Intervention Type: DRUG

600mg once daily for 96 weeks

TMC278

TMC278 25 mg tablet once daily for 96 weeks

Group Type: EXPERIMENTAL

TMC278

Intervention Type: DRUG

25 mg tablet once daily for 96 weeks

Interventions

TMC278

25 mg tablet once daily for 96 weeks

Intervention Type: DRUG

Efavirenz

600mg once daily for 96 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient with documented HIV-1 infection
• Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening
• Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure)
• Patient's virus is sensitive to TDF and FTC
• Patient agrees not to start ART (antiretroviral treatment) before the baseline visit

Exclusion Criteria

• Previous use of ANY ARV drug for ANY length of time
• Any documented evidence of NNRTI resistance associated mutations in patient's HIV
• Category C AIDS defining illness, except: stable Kaposi Sarcoma, wasting syndrome if not progressive
• Pneumocystis carinii pneumonia (PCP) that is considered not cured
• Active TB
• Allergy or hypersensitivity to study or background ARTs
• Specific grade 3 or 4 toxicity
• Kidney impairment: calculated creatinine clearance <50 ml/min

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec Pharmaceuticals Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceutical Limited

Locations

Birmingham, Alabama, United States

Phoenix, Arizona, United States

Beverly Hills, California, United States

Los Angeles, California, United States

Newport Beach, California, United States

Sacramento, California, United States

Washington D.C., District of Columbia, United States

Fort Lauderdale, Florida, United States

Miami, Florida, United States

Tampa, Florida, United States

Vero Beach, Florida, United States

West Palm Beach, Florida, United States

Macon, Georgia, United States

Chicago, Illinois, United States

Baltimore, Maryland, United States

Newark, New Jersey, United States

Albany, New York, United States

Buffalo, New York, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Durham, North Carolina, United States

Winston-Salem, North Carolina, United States

Akron, Ohio, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Portland, Oregon, United States

Philadelphia, Pennsylvania, United States

Columbia, South Carolina, United States

Austin, Texas, United States

Dallas, Texas, United States

Seattle, Washington, United States

Milwaukee, Wisconsin, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Guernica, , Argentina

Darlinghurst, , Australia

Melbourne, , Australia

Perth, , Australia

Surry Hills, , Australia

Innsbruck, , Austria

Vienna, , Austria

Curitiba, , Brazil

Nova Iguaçu, , Brazil

Rio de Janeiro, , Brazil

Salvador, , Brazil

São Paulo, , Brazil

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Copenhagen, , Denmark

Hvidovre, , Denmark

Odense, , Denmark

Loiré, , France

Lyon, , France

Paris, , France

Tourcoing, , France

Villejuif, , France

Mexico City, , Mexico

Zapopan, , Mexico

Rotterdam, , Netherlands

Amadora, , Portugal

Lisbon, , Portugal

Portimão, , Portugal

Porto, , Portugal

San Juan, , Puerto Rico

Bucharest, , Romania

Iași, , Romania

Timișoara, , Romania

Krasnodar, , Russia

Saint Petersburg, , Russia

Bloemfontein, , South Africa

Cape Town, , South Africa

Durban, , South Africa

Houghton, Johannesburg, , South Africa

Johannesburg, , South Africa

Pretoria, , South Africa

Alicante, , Spain

Barcelona, , Spain

Madrid, , Spain

Gothenburg, , Sweden

Malmo, , Sweden

Stockholm, , Sweden

Kaohsiung City, , Taiwan

Kaohsiung County, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

Bangkok, , Thailand

Chiang Mai, , Thailand

Khon Kaen, , Thailand

Birmingham, , United Kingdom

Brighton, , United Kingdom

London, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Brazil; Canada; Denmark; France; Mexico; Netherlands; Portugal; Puerto Rico; Romania; Russia; South Africa; Spain; Sweden; Taiwan; Thailand; United Kingdom

References

Rimsky L, Van Eygen V, Hoogstoel A, Stevens M, Boven K, Picchio G, Vingerhoets J. 96-Week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE Phase III trials. Antivir Ther. 2013;18(8):967-77. doi: 10.3851/IMP2636. Epub 2013 May 28.

Reference Type: DERIVED

PMID: 23714781 (View on PubMed)

Nelson M, Amaya G, Clumeck N, Arns da Cunha C, Jayaweera D, Junod P, Li T, Tebas P, Stevens M, Buelens A, Vanveggel S, Boven K; ECHO and THRIVE Study Groups. Efficacy and safety of rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III randomized, double-blind ECHO and THRIVE trials. J Antimicrob Chemother. 2012 Aug;67(8):2020-8. doi: 10.1093/jac/dks130. Epub 2012 Apr 24.

Reference Type: DERIVED

PMID: 22532465 (View on PubMed)

Molina JM, Cahn P, Grinsztejn B, Lazzarin A, Mills A, Saag M, Supparatpinyo K, Walmsley S, Crauwels H, Rimsky LT, Vanveggel S, Boven K; ECHO study group. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011 Jul 16;378(9787):238-46. doi: 10.1016/S0140-6736(11)60936-7.

Reference Type: DERIVED

PMID: 21763936 (View on PubMed)

Other Identifiers

TMC278-TIDP6-C209

Identifier Type: OTHER

Identifier Source: secondary_id

CR002689

Identifier Type: -

Identifier Source: org_study_id

NCT00613639

Identifier Type: -

Identifier Source: nct_alias