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

Tibotec Pharmaceutical

Status and phase: Completed; Phase 2

Conditions: Human Immunodeficiency Virus Type 1

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00110305

TMC278-C204 (Other Identifier)

R278474-C204 (Other Identifier)

CR006760

Details and patient eligibility

About

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.

Full 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.

Enrollment: 368 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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368 participants in 4 patient groups

TMC278 25 mg

Experimental group

Description:

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.

Treatment:

Drug: TMC278 25 mg

Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

TMC278 75 mg

Experimental group

Description:

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.

Treatment:

Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Drug: TMC278 75 mg

TMC278 150 mg

Experimental group

Description:

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.

Treatment:

Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Drug: TMC278 150 mg

Efavirenz

Active Comparator group

Description:

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.

Treatment:

Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Drug: Efavirenz