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

Condition(s) targeted: Human Immunodeficiency Virus Type 1

Intervention: TMC278 25 mg (Drug); TMC278 75 mg (Drug); TMC278 150 mg (Drug); Efavirenz (Drug); Non-nucleoside reverse transcriptase inhibitor (NRTIs) (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Tibotec Pharmaceuticals, Ireland

Official(s) and/or principal investigator(s):
Tibotec Pharmaceuticals, Ireland Clinical Trial, Study Director, Affiliation: Tibotec Pharmaceuticals, Ireland

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.

Official title: A Phase IIb Randomized, Partially Blinded, Dose-Finding Trial of TMC278 in Antiretroviral-Naive HIV-1 Infected Subjects

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

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

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

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

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

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

Change From Baseline in CD4+ Cell Count (Absolute) at Week 96

Change From Baseline in CD4+ Cell Count (Relative) at Week 96

Change From Baseline in CD4+ Cell Count (Absolute) at Week 240

Change From Baseline in CD4+ Cell Count (Relative) at Week 240

Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure

Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278

Trough Plasma Concentration (Ctrough) for TMC278

Number of Participants With Virologic Response (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm, by Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) Quartiles

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Buenos Aires, Argentina

Rosario, Argentina

Wien, Austria

Campinas, Brazil

Curitiba, Brazil

Pinheiros, Brazil

Rio De Janeiro, Brazil

Sao Paulo, Brazil

Beijing, China

Paris Cedex 10, France

Paris Cedex 12, France

Paris, France

Tourcoing, France

Berlin, Germany

Freiburg, Germany

Köln, Germany

München, Germany

Ciudad De Mexico, Mexico

San Juan, Puerto Rico

Kazan, Russian Federation

Moscow N/A, Russian Federation

Moscow, Russian Federation

Nizhny Novgorod, Russian Federation

Saint-Petersburg, Russian Federation

St Petersburg, Russian Federation

Volgograd, Russian Federation

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

Beverly Hills, California, United States

Washington, 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

Starting date: June 2005
Last updated: June 11, 2014