TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

This study has been completed.
Sponsor:
Information provided by:
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00543725
First received: October 11, 2007
Last updated: May 14, 2012
Last verified: May 2012

October 11, 2007
May 14, 2012
May 2008
January 2010   (final data collection date for primary outcome measure)
Virological Response[ITT - TLOVR,<50 Copies/mL] [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Virological response is defined as confirmed plasma viral load < 50 HIV-1 (RNA) copies/mL at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and subjects who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes subjects who were rebounder (confirmed viral load >= 50 copies/mL after being responder) or who were never suppressed (no confirmed viral load <50 copies/mL)
Result of TMC278 is comparative to efavirez (EFV) for proportion of patients with plasma VL < 50 HIV-1 RNA copies/mL (TLOVR algorithm) at week 48 (visit number 11 of 16 total study visits)
Complete list of historical versions of study NCT00543725 on ClinicalTrials.gov Archive Site
Virological Response[ITT - Snapshot,<50 Copies/mL] [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/mL (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/mL in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/mL, and subjects who had a switch in background regimen that was not permitted by the protocol.
Safety and tolerability evaluation, compare antiviral activity, immunologic changes, assess viral geno- and phenotype over 96 weeks. Population PK and preference based health states and adherence assessment, Optional PK and DEXAscan substudies.
Not Provided
Not Provided
 
TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
A Phase III, Randomized, Double-blind Trial of TMC278 25mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Background Regimen Containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-naive HIV-1 Infected Subjects.

The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) in HIV-1 infected patients who have not yet taken any anti-HIV drugs. The following evaluations will be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution, relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics and Medical resource utilization and treatment adherence.

Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced sequentially for use in the clinic. Currently, patients are routinely being treated with 3 or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This is a Phase III, randomized (study medication is assigned by chance), double-blind (neither the study physician nor the patient knows the name of the study assigned medication), double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up period. Patients will be randomly assigned (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors. The hypothesis to be provided in this study is that the investigational drug TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e., suppressing of the plasma viral load to a level < 50 HIV-1 RNA (ribonucleic acid) copies/mL, in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by physical examination, interview to assess health and well being, and laboratory testing on blood and urine samples. Experimental Group: One tablet of TMC278 25 mg daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase inhibitors for 104 weeks.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV Infections
  • HIV-1
  • Drug: TMC278
    25 mg tablet once daily for 96 weeks
  • Drug: efavirenz
    600 mg tablet once daily for 96 weeks
  • Active Comparator: 002
    efavirenz 600 mg tablet once daily for 96 weeks
    Intervention: Drug: efavirenz
  • Experimental: 001
    TMC278 25 mg tablet once daily for 96 weeks
    Intervention: Drug: TMC278

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
680
February 2012
January 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient with documented HIV-1 infection
  • Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening
  • Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure)
  • Patient's virus is sensitive to the 2 nucleoside/nucleotide reverse transcriptase inhibitors chosen for treatment
  • Patient agrees not to start ART before the baseline visit
  • Patient is HLA-B*5701 negative in case abacavir is included in the patient's treatment regimen.

Exclusion Criteria:

  • Previous use of ANY ARV drug for ANY length of time
  • Any documented evidence of NNRTI resistance associated mutations in patient's HIV
  • Category C AIDS defining illness, except, Stable Kaposi Sarcoma Wasting syndrome if not progressive
  • Pneumocystis carinii pneumonia (PCP) that is considered not cured
  • Active TB
  • Allergy or hypersensitivity to study or background ARTs
  • Specific grade 3 or 4 toxicity
  • Kidney impairment: calculated creatinine clearance <50 ml/min
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
China,   United States,   Australia,   Belgium,   Brazil,   Canada,   Chile,   United Kingdom,   Costa Rica,   France,   Germany,   India,   Mexico,   Panama,   Portugal,   Puerto Rico,   Russian Federation,   South Africa,   Spain,   Thailand
 
NCT00543725
CR002704, TMC278-TIDP6-C215
Yes
Compound Development Team Leader TMC278, Tibotec Pharmaceutical Limited
Tibotec Pharmaceuticals, Ireland
Not Provided
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
Tibotec Pharmaceuticals, Ireland
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP