TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

NCT ID: NCT00543725

Last Updated: 2016-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 680 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2012-02-29

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 background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) 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 and 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 (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors. 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 daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase inhibitors for 104 weeks.

Conditions

HIV Infections; HIV-1

Study Design

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

Study Groups

002

efavirenz 600 mg tablet once daily for 96 weeks

Group Type: ACTIVE_COMPARATOR

efavirenz

Intervention Type: DRUG

600 mg tablet once daily for 96 weeks

001

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

600 mg tablet 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 the 2 nucleoside/nucleotide reverse transcriptase inhibitors chosen for treatment
• Patient agrees not to start ART before the baseline visit
• Patient is HLA-B*5701 negative in case abacavir is included in the patient's treatment regimen.

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, Ireland Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceuticals, Ireland

Locations

Long Beach, California, United States

Los Angeles, California, United States

San Francisco, California, United States

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

Atlantis, Florida, United States

Miami, Florida, United States

Miami Beach, Florida, United States

Orlando, Florida, United States

Tampa, Florida, United States

Chicago, Illinois, United States

Lexington, Kentucky, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

Springfield, Massachusetts, United States

Detroit, Michigan, United States

Minneapolis, Minnesota, United States

Newark, New Jersey, United States

Flushing, New York, United States

New York, New York, United States

Rochester, New York, United States

The Bronx, New York, United States

Philadelphia, Pennsylvania, United States

Dallas, Texas, United States

Houston, Texas, United States

Longview, Texas, United States

Darlinghurst, , Australia

Prahran, , Australia

Surry Hills, , Australia

Antwerp, , Belgium

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Campinas, , Brazil

Distrito Barao Geraldo-Campina, , Brazil

Pinheiros, , Brazil

Recife, , Brazil

São Paulo, , Brazil

Calgary, Alberta, Canada

Vancouver, British Columbia, Canada

Winnipeg, Manitoba, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Providencia, , Chile

Santiago, , Chile

Beijing, , China

Guangzhou, , China

Shanghai, , China

San José, , Costa Rica

Clamart, , France

Le Kremlin-Bicêtre, , France

Montpellier, , France

Paris, , France

Berlin, , Germany

Cologne, , Germany

Essen, , Germany

Frankfurt, , Germany

Hamburg, , Germany

Hanover, , Germany

Mannheim, , Germany

Chennai, , India

Nagpur, , India

Guadalajara, , Mexico

Mexico City, , Mexico

Panama City, , Panama

Porto, , Portugal

San Juan, , Puerto Rico

Moscow, , Russia

Saint Petersburg, , Russia

Smolensk, , Russia

Voronezh, , Russia

Bloemfontein, , South Africa

Cape Town, , South Africa

Dundee, , South Africa

Johannesburg, , South Africa

Pretoria, , South Africa

Westdene Johannesburg Gauteng, , South Africa

Barcelona, , Spain

Elche, , Spain

Madrid, , Spain

Bangkok, , Thailand

London, , United Kingdom

Manchester, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; Canada; Chile; China; Costa Rica; France; Germany; India; Mexico; Panama; Portugal; Puerto Rico; Russia; South Africa; Spain; 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)

Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, Johnson MA, Ruxrungtham K, Wu H, Zorrilla C, Crauwels H, Rimsky LT, Vanveggel S, Boven K; THRIVE study group. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011 Jul 16;378(9787):229-37. doi: 10.1016/S0140-6736(11)60983-5.

Reference Type: DERIVED

PMID: 21763935 (View on PubMed)

Other Identifiers

TMC278-TIDP6-C215

Identifier Type: OTHER

Identifier Source: secondary_id

CR002704

Identifier Type: -

Identifier Source: org_study_id

NCT00614692

Identifier Type: -

Identifier Source: nct_alias