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TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.

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ClinicalTrials.gov Identifier: NCT00540449
Recruitment Status : Completed
First Posted : October 8, 2007
Results First Posted : July 11, 2011
Last Update Posted : March 29, 2016
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland

Tracking Information
First Submitted Date  ICMJE October 4, 2007
First Posted Date  ICMJE October 8, 2007
Results First Submitted Date  ICMJE June 14, 2011
Results First Posted Date  ICMJE July 11, 2011
Last Update Posted Date March 29, 2016
Study Start Date  ICMJE May 2008
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2015)
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 [ Time Frame: Week 48 ]
Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).
Original Primary Outcome Measures  ICMJE
 (submitted: October 4, 2007)
Non-inferiority of TMC278 versus control (EFV) for proportion of patients with plasma VL < 50 HIV-1 RNA copies/mL (TLOVR algorithm) at week 48.
Change History Complete list of historical versions of study NCT00540449 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2016)
  • The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 [ Time Frame: Week 48 ]
    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.
  • Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 [ Time Frame: Week 96 ]
  • The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 [ Time Frame: Week 96 ]
  • Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96). [ Time Frame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit ]
    Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per ml at the last on-treatment visit (post-Week 96).
  • Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48 [ Time Frame: Week 48 ]
  • Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96 [ Time Frame: Week 96 ]
  • Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) [ Time Frame: Baseline, Week 48, and Week 96 ]
    Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
  • Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure [ Time Frame: Week 96 ]
    Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load <50 copies/mL) and plasma viral load increase of >=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Original Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2007)
Evaluate safety and tolerabilty over 96 weeks; Compare antiviral activity, immunologic changes, assess viral geno- and phenotype over 96 weeks; Population PK; Assess preference based health states and adherence; Optional PK and DEXAscan substudies.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.
Official Title  ICMJE A Phase III, Randomized, Double-blind Trial of TMC278 25 mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Fixed Background Regimen Consisting of Tenofovir Disoproxil Fumarate and Emtricitabine in Antiretroviral-naive HIV-1 Infected Subjects.
Brief Summary 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 fixed background regimen consisting of emtricitabine (FTC) + tenofovir disoproxil fumarate (TDF), 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, medical resource utilization and treatment adherence.
Detailed Description 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 to TMC278 or to efavirenz, either of these treatments will be in combination with two other anti-HIV drugs (2 NRTIs: emtricitabine (FTC) + tenofovir (TDF)). TDF/FTC will be administered as a fixed dose combination if available. 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 once daily plus one tablet of placebo once daily that looks just like efavirenz (EFV) plus tenofovir/emtricitabine; Control Group: One tablet of Placebo once daily that looks just like TMC278 plus EFV 600 mg once daily plus tenofovir/emtricitabine.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV Infections
  • HIV-1
  • Human Immunodeficiency Virus Type 1
Intervention  ICMJE
  • Drug: TMC278
    25 mg tablet once daily for 96 weeks
  • Drug: Efavirenz
    600mg once daily for 96 weeks
Study Arms  ICMJE
  • Active Comparator: Efavirenz
    Efavirenz 600mg once daily for 96 weeks
    Intervention: Drug: Efavirenz
  • Experimental: TMC278
    TMC278 25 mg tablet once daily for 96 weeks
    Intervention: Drug: TMC278
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 20, 2012)
694
Original Enrollment  ICMJE
 (submitted: October 4, 2007)
680
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 TDF and FTC
  • Patient agrees not to start ART (antiretroviral treatment) before the baseline visit

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Brazil,   Canada,   Denmark,   France,   Mexico,   Netherlands,   Portugal,   Puerto Rico,   Romania,   Russian Federation,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   United Kingdom,   United States
Removed Location Countries India,   Uganda
 
Administrative Information
NCT Number  ICMJE NCT00540449
Other Study ID Numbers  ICMJE CR002689
TMC278-TIDP6-C209 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tibotec Pharmaceuticals, Ireland
Study Sponsor  ICMJE Tibotec Pharmaceuticals, Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
PRS Account Tibotec Pharmaceuticals, Ireland
Verification Date February 2016

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