Clinical Trials


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

This study has been completed
Tibotec Pharmaceuticals, Ireland

Information provided by (Responsible Party)
Tibotec Pharmaceuticals, Ireland Identifier

First received: October 4, 2007
Last updated: March 1, 2016
Last Verified: February 2016
History of Changes


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.

Condition Intervention Phase
HIV Infections
Human Immunodeficiency Virus Type 1

Drug : TMC278
Drug : Efavirenz
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-blind Trial of TMC278 25 mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Fixed Background Regimen Consisting of Tenofovir Disoproxil Fumarate and Emtricitabine in Antiretroviral-naive HIV-1 Infected Subjects.

Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures

  • Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 [ Time Frame: Week 48 ]
    Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).
Secondary Outcome Measures:
  • The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 [ Time Frame: Week 48 ]
    The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/ml (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/ml in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/ml and subjects who had a switch in background regimen that was not permitted by the protocol.
  • Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 [ Time Frame: Week 96 ]
  • The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 [ Time Frame: Week 96 ]
  • Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96). [ Time Frame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit ]
    Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per ml at the last on-treatment visit (post-Week 96).
  • Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48 [ Time Frame: Week 48 ]
  • Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96 [ Time Frame: Week 96 ]
  • Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) [ Time Frame: Baseline, Week 48, and Week 96 ]
    Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
  • Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure [ Time Frame: Week 96 ]
    Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load <50 copies/mL) and plasma viral load increase of >=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).

Enrollment: 694
Study Start Date: May 2008
Study Completion Date: December 2011
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: Efavirenz
Efavirenz 600mg once daily for 96 weeks
Drug: Efavirenz

600mg once daily for 96 weeks

Experimental: TMC278
TMC278 25 mg tablet once daily for 96 weeks
Drug: TMC278

25 mg tablet once daily for 96 weeks

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.



Ages Eligible for Study: 18 Years to 99 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  


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

contacts and locations

Contacts and Locations

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Please refer to this study by its identifier: NCT00540449


United States, Alabama
Birmingham, Alabama, United States
United States, Arizona
Phoenix, Arizona, United States
United States, California
Beverly Hills, California, United States
Los Angeles, California, United States
Newport Beach, California, United States
Sacramento, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Fort Lauderdale, Florida, United States
Miami, Florida, United States
Tampa, Florida, United States
Vero Beach, Florida, United States
West Palm Beach, Florida, United States
United States, Georgia
Macon, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Maryland
Baltimore, Maryland, United States
United States, New Jersey
Newark, New Jersey, United States
United States, New York
Albany, New York, United States
Buffalo, New York, United States
New York, New York, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
Durham, North Carolina, United States
Winston Salem, North Carolina, United States
United States, Ohio
Akron, Ohio, United States
Cincinnati, Ohio, United States
Columbus, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, South Carolina
Columbia, South Carolina, United States
United States, Texas
Austin, Texas, United States
Dallas, Texas, United States
United States, Washington
Seattle, Washington, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Buenos Aires, Argentina
Cordoba, Argentina
Guernica, Argentina
Darlinghurst, Australia
Melbourne, Australia
Perth, Australia
Surry Hills, Australia
Innsbruck, Austria
Vienna, Austria
Wien, Austria
Curitiba, Brazil
Nova Iguacu, Brazil
Rio De Janeiro, Brazil
Salvador, Brazil
Sao Paulo, Brazil
Ottawa, Ontario, Canada
Toronto, Ontario, Canada
Montreal, Quebec, Canada
Copenhagen, Denmark
Hvidovre N/A, Denmark
Odense N/A, Denmark
Loire, France
Lyon, France
Paris Cedex 10, France
Paris Cedex 12, France
Paris, France
Tourcoing, France
Villejuif Cedex, France
Ciudad De Mexico, Mexico
Zapopan, Mexico
Rotterdam, Netherlands
Amadora, Portugal
Lisboa, Portugal
Portimao, Portugal
Porto, Portugal
Puerto Rico
San Juan, Puerto Rico
Bucuresti, Romania
Iasi, Romania
Timisoara, Romania
Russian Federation
Krasnodar, Russian Federation
St Petersburg, Russian Federation
South Africa
Bloemfontein, South Africa
Cape Town, South Africa
Durban N/A, South Africa
Houghton, Johannesburg, South Africa
Johannesburg, South Africa
Pretoria N/A, South Africa
Alicante, Spain
Barcelona, Spain
Madrid, Spain
Göteborg, Sweden
Malmö, Sweden
Stockholm, Sweden
Kaohsiung County, Taiwan
Kaohsiung, Taiwan
Tainan, Taiwan
Taipei, Taiwan
Bangkok, Thailand
Chiang Mai, Thailand
Khon Kaen, Thailand
United Kingdom
Birmingham, United Kingdom
Brighton, United Kingdom
London, United Kingdom

Sponsors and Collaborators

Tibotec Pharmaceuticals, Ireland


Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
More Information

More Information

Responsible Party: Tibotec Pharmaceuticals, Ireland Identifier: NCT00540449   History of Changes  
Other Study ID Numbers: CR002689  
Study First Received: October 4, 2007  
Last Updated: March 1, 2016  

Keywords provided by Tibotec Pharmaceuticals, Ireland:

Non-nucleoside reverse transcriptase inhibitor
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
Rilpivirine processed this data on July 20, 2018
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