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

NCT ID: NCT00110305

Last Updated: 2014-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 368 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2011-12-31

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.

Detailed Description

This is a randomized (the study medication is assigned by chance), active controlled (participants are assigned to either a recognized effective treatment or the study medication) study. This study consists of 3 phases: screening phase (4 weeks), treatment phase (96 weeks), and follow up phase (4 weeks). In the treatment phase, participants will be randomly assigned to 1 of the 4 treatment groups: (1) TMC278 25 mg, (2) TMC278 75 mg, (3) TMC278 150 mg, or (4) efavirnez (control group); along with investigator selected 2 non-nucleoside reverse transcriptase inhibitor (NRTIs) until Week 96. TMC278 will be assigned by double-blinded fashion (participant and investigator are not aware of the TMC278 dose what participants will receive) and efavirnez will be assigned by open-label fashion (all people know what treatment participants will receive). After Week 96, 3 optional open-label (all people know the identity of the intervention) extension periods will be conducted to collect long term safety and effectiveness data of TMC278. 3 optional extension periods are: first optional extension period (all participants will receive TMC278 75 mg + 2 NRTIs from Week 96 to Week144); second optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 144 to Week 240); and third optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 240 until TMC278 is commercially available). Participants on efavirenz group will have the option to continue on efavirenz + 2 NRTIs until the total treatment duration of 240 weeks. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, physical examination, and vital signs which will be monitored throughout the study. The maximum duration of the study will be 104, 152, or 248 weeks, plus the optional third extension period.

Conditions

Human Immunodeficiency Virus Type 1

Study Design

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

Study Groups

TMC278 25 mg

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.

Group Type: EXPERIMENTAL

TMC278 25 mg

Intervention Type: DRUG

TMC278 25 mg tablet will be administered once daily.

Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Intervention Type: 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.

TMC278 75 mg

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.

Group Type: EXPERIMENTAL

TMC278 75 mg

Intervention Type: DRUG

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

Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Intervention Type: 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.

TMC278 150 mg

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.

Group Type: EXPERIMENTAL

TMC278 150 mg

Intervention Type: DRUG

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

Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Intervention Type: 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.

Efavirenz

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.

Group Type: ACTIVE_COMPARATOR

Efavirenz

Intervention Type: 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.

Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Intervention Type: 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.

Interventions

TMC278 25 mg

TMC278 25 mg tablet will be administered once daily.

Intervention Type: DRUG

TMC278 75 mg

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

Intervention Type: DRUG

TMC278 150 mg

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

Intervention Type: DRUG

Efavirenz

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

Intervention Type: DRUG

Non-nucleoside reverse transcriptase inhibitor (NRTIs)

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.

Intervention Type: DRUG

Other Intervention Names

Combivir; Truvada

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 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

Beverly Hills, California, United States

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

Orlando, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Stony Brook, New York, United States

Winston-Salem, North Carolina, United States

Addison, Texas, United States

Seattle, Washington, United States

Buenos Aires, , Argentina

Rosario, , Argentina

Vienna, , Austria

Campinas, , Brazil

Curitiba, , Brazil

Pinheiros, , Brazil

Rio de Janeiro, , Brazil

São Paulo, , Brazil

Beijing, , China

Paris, , France

Tourcoing, , France

Berlin, , Germany

Cologne, , Germany

Freiburg im Breisgau, , Germany

München, , Germany

Mexico City, , Mexico

San Juan, , Puerto Rico

Kazan', , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Saint Petersburg, , Russia

Volgograd, , Russia

Bloemfontein, , South Africa

Cape Town, , South Africa

Johannesburg, , South Africa

Bangkok, , Thailand

Chiang Mai, , Thailand

Khon Kaen, , Thailand

Kampala, , Uganda

London, , United Kingdom

Manchester, , United Kingdom

Countries

United States; Argentina; Austria; Brazil; China; France; Germany; Mexico; Puerto Rico; Russia; South Africa; Thailand; Uganda; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 19926964 (View on PubMed)

Other Identifiers

TMC278-C204

Identifier Type: OTHER

Identifier Source: secondary_id

R278474-C204

Identifier Type: OTHER

Identifier Source: secondary_id

CR006760

Identifier Type: -

Identifier Source: org_study_id

NCT00980837

Identifier Type: -

Identifier Source: nct_alias