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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.

This study has been completed.
Sponsor:
Information provided by:
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00540449
First received: October 4, 2007
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
HIV-1
Human Immunodeficiency Virus Type 1
Drug: TMC278
Drug: efavirenz
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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.


Enrollment: 694
Study Start Date: April 2008
Study Completion Date: December 2011
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 002
efavirenz 600mg once daily for 96 weeks
Drug: efavirenz
600mg once daily for 96 weeks
Experimental: 001
TMC278 25 mg tablet once daily for 96 weeks
Drug: TMC278
25 mg tablet once daily for 96 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00540449

  Show 91 Study Locations
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided by Tibotec Pharmaceuticals, Ireland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Compound Development Team Leader TMC278, Tibotec Pharmaceutical Limited
ClinicalTrials.gov Identifier: NCT00540449     History of Changes
Obsolete Identifiers: NCT00613639
Other Study ID Numbers: CR002689, TMC278-TIDP6-C209
Study First Received: October 4, 2007
Results First Received: June 14, 2011
Last Updated: October 25, 2012
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority
Canada: Health Canada
Great Britain: Medicines and Healthcare Products Regulatory Agency
Taiwan: Department of Health

Keywords provided by Tibotec Pharmaceuticals, Ireland:
TMC278-C209
Antiretroviral
Non-nucleoside reverse transcriptase inhibitor
HIV-1
AIDS
TMC278-TiDP6-C209
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Efavirenz
Emtricitabine
Reverse Transcriptase Inhibitors
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014