A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines

NCT00110305 | Completed Phase 2 Results DMC

• 3 other identifiers: CR006760TMC278-C204R278474-C204
• Study Type: interventional
• Target: 368
• Locations: 14 countries
• Sites: 40

Brief Summary

The purpose of this study is to evaluate the dose-response relationship of antiviral activity after 48 weeks treatment with 3 different dose regimens of TMC278.

Conditions

Human Immunodeficiency Virus Type 1

Keywords

Human Immunodeficiency Virus Type 1; Human immunodeficiency virus (HIV); Antiretroviral; Antiviral; ARV; TMC278; Efavirenz; Combivir; Truvada; Zidovudine; Lamivudine; Tenofovir disoproxil fumarate; Emtricitabine

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm

  The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.

  Week 48

Secondary Outcomes (13)

• Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm

  Week 96

• Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis

  Week 96

• Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm

  Week 240

• Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis

  Week 240

• Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 400 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm

  Week 240

Study Arms (4)

TMC278 25 mg

EXPERIMENTAL

Participants will receive TMC278 25 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.

Drug: TMC278 25 mg; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

TMC278 75 mg

EXPERIMENTAL

Participants will receive TMC278 75 mg once daily up to Week 144. Later on, participants will receive TMC278 25 mg once daily up to Week 240.

Drug: TMC278 75 mg; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

TMC278 150 mg

EXPERIMENTAL

Participants will receive TMC278 150 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.

Drug: TMC278 150 mg; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Efavirenz

ACTIVE COMPARATOR

Participants will receive efavirenz 600 mg once daily up to Week 96. Later on, participants will have an option to continue on efavirenz until Week 144 or until Week 240.

Drug: Efavirenz; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Interventions

TMC278 25 mg DRUG

TMC278 25 mg tablet will be administered once daily.

TMC278 25 mg

TMC278 75 mg DRUG

TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.

TMC278 75 mg

TMC278 150 mg DRUG

TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.

TMC278 150 mg

Efavirenz DRUG

Efavirenz 600 mg (1 x 600 mg tablet or 3 x 200 mg capsules, depending on formulation locally available) will be administered once daily.

Efavirenz

Non-nucleoside reverse transcriptase inhibitor (NRTIs) DRUG

Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.

Also known as: Combivir, Truvada

Efavirenz; TMC278 150 mg; TMC278 25 mg; TMC278 75 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented human immunodeficiency virus type 1 (HIV-1) infection
• Never been treated with an antiretroviral (ARV) treatment or therapeutic HIV vaccine, or received less than or equal to 2 weeks treatment prior to screening with an nucleoside reverse transcriptase inhibitors
• HIV-1 plasma viral load above 5000 HIV-1 RNA copies per milliliter, at screening
• Cortisol of at least 550 nano moles per liter (19.9 microgram per deciliter) at screening
• Sensitivity to investigator selected nucleosides, at screening

You may not qualify if:

• Currently having active Acquired Immunodeficiency Syndrome (AIDS) defining illness
• Known or suspected acute (primary) HIV-1 infection
• Any current or history of adrenal disorder, and an acute hepatitis A, B, or C infection
• Documented genotypic evidence of Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) resistance at screening
• Pregnant or breastfeeding females
• Not agree to protocol-defined effective use of contraception

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Study Sites (40)

Unknown Facility

Beverly Hills, California, United States

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

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Stony Brook, New York, United States

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Winston-Salem, North Carolina, United States

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Addison, Texas, United States

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Seattle, Washington, United States

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Buenos Aires, Argentina

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Rosario, Argentina

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Vienna, Austria

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Campinas, Brazil

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Curitiba, Brazil

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Pinheiros, Brazil

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Beijing, China

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Paris, France

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Tourcoing, France

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Berlin, Germany

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Cologne, Germany

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Freiburg im Breisgau, Germany

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München, Germany

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Mexico City, Mexico

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San Juan, Puerto Rico

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Kazan', Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Saint Petersburg, Russia

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Volgograd, Russia

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Bloemfontein, South Africa

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Cape Town, South Africa

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Johannesburg, South Africa

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Bangkok, Thailand

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Chiang Mai, Thailand

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Khon Kaen, Thailand

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Kampala, Uganda

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London, United Kingdom

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Manchester, United Kingdom

Location

Related Publications (1)

• Pozniak AL, Morales-Ramirez J, Katabira E, Steyn D, Lupo SH, Santoscoy M, Grinsztejn B, Ruxrungtham K, Rimsky LT, Vanveggel S, Boven K; TMC278-C204 Study Group. Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial. AIDS. 2010 Jan 2;24(1):55-65. doi: 10.1097/QAD.0b013e32833032ed.

  PMID: 19926964 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Rilpivirine; efavirenz; lamivudine, zidovudine drug combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Director
• Organization: Janssen-Virco BE

32 14 641418

Study Officials

• Tibotec Pharmaceuticals, Ireland Clinical Trial

  Tibotec Pharmaceuticals, Ireland

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2005
• First Posted: May 6, 2005
• Study Start: June 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: June 25, 2014
• Results First Posted: October 28, 2013

Record last verified: 2014-06

Locations

PR (1); GB (2); ME (1); CN (1); ZA (3); BR (5); AU (1); AR (2); DE (4); RU (5); US (9); FR (2); TH (3); UG (1)