Clinical trial NCT00110305: A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines
Official title: A Phase IIb Randomized, Partially Blinded, Dose-Finding Trial of TMC278 in Antiretroviral-Naive HIV-1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2005-05-06
Enrollment: 368
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: Week 48
Secondary outcomes:
measure: 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
timeFrame: Week 96
measure: Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
timeFrame: Week 96
measure: 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
timeFrame: Week 240
measure: Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
timeFrame: Week 240
measure: 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
timeFrame: Week 240
measure: Change From Baseline in CD4+ Cell Count (Absolute) at Week 96
timeFrame: Baseline (Day 1 of Week 0) to Week 96
measure: Change From Baseline in CD4+ Cell Count (Relative) at Week 96
timeFrame: Baseline (Day 1 of Week 0) to Week 96
measure: Change From Baseline in CD4+ Cell Count (Absolute) at Week 240
timeFrame: Baseline (Day 1 of Week 0) to Week 240
measure: Change From Baseline in CD4+ Cell Count (Relative) at Week 240
timeFrame: Baseline (Day 1 of week 0) to Week 240
measure: Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
timeFrame: Week 240
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278
timeFrame: Up to Week 96
measure: Trough Plasma Concentration (Ctrough) for TMC278
timeFrame: Up to Week 96
measure: 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
timeFrame: Up to Week 96
Other outcomes:
Locations:
city: Beverly Hills
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Stony Brook
country: United States
state: New York
city: Winston-Salem
country: United States
state: North Carolina
city: Addison
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Rosario
country: Argentina
city: Wien
country: Austria
city: Campinas
country: Brazil
city: Curitiba
country: Brazil
city: Pinheiros
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Beijing
country: China
city: Paris Cedex 10
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Tourcoing
country: France
city: Berlin
country: Germany
city: Freiburg
country: Germany
city: Köln
country: Germany
city: München
country: Germany
city: Ciudad De Mexico
country: Mexico
city: San Juan
country: Puerto Rico
city: Kazan
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: Johannesburg
country: South Africa
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Kampala
country: Uganda
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.