TMC125-C206: A Phase III Study to Investigate the Efficacy, Tolerability and Safety of TMC125 as Part of an Antiretroviral Regimen, Including TMC114/Ritonavir and an Investigator-selected Optimized Background, in HIV-1 Infected Patients With Limited to no Treatment Options.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00254046
First received: November 10, 2005
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

The purpose of this study is research with the goal of evaluating the effect of TMC125 (a non-nucleoside reverse transcriptase inhibitor) on slowing down the growth of the HIV virus. The study will also investigate whether this new medication is well tolerated, and to further confirm that the medication is safe to be used.


Condition Intervention Phase
HIV
Drug: TMC125
Drug: Placebo
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-blinded, Placebo-controlled Trial to Investigate the Efficacy, Tolerability and Safety of TMC125 as Part of an ART Regimen, Including TMC114/RTV and an Investigator-selected OBR, in HIV-1 Infected Patients With Limited Treatment to no Treatment Options.

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Evaluation of efficacy, tolerability and safety of TMC125 as part of an antiretroviral therapy containing TMC114/ritonavir and an investigator selected optimized background regimen. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 616
Study Start Date: November 2005
Study Completion Date: July 2008
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 002
Placebo 2 tablets b.i.d.96 weeks
Drug: Placebo
2 tablets b.i.d.96 weeks
Active Comparator: 001
TMC125 2 X100 mg tablets b.i.d.96 weeks
Drug: TMC125
2 X100 mg tablets b.i.d.96 weeks

Detailed Description:

This is a Phase III, randomized, double-blind, placebo-controlled trial to evaluate the long-term efficacy, tolerability, and safety of TMC125 as part of an antiretroviral therapy (ART) regimen containing TMC114/ritonavir (RTV) and an investigator-selected optimized background (OBR) in treatment-experienced HIV-1 infected patients. TMC125 is a non-nucleoside reverse transcriptase inhibitor (NNRTI). TMC114 is a protease inhibitor (PI). In this trial, TMC114 will be given with a low dose of ritonavir (RTV), a protease inhibitor commonly used with other, full dose protease inhibitors to improve activity. Additional assessment to be evaluated in this trial include: changes in the HIV-1 genotype, drug susceptibility, and the population pharmacokinetics of TMC125. A pharmacokinetic substudy will be performed at selected sites. Health-related quality of life will be assessed for patients receiving an antiretroviral therapy containing either TMC125 or placebo. Safety and tolerability will be documented throughout the trial. Six hundred HIV-1 infected patients on a stable but virologically failing regimen will be included in the trial. Patients should have at least 1 documented non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation (either at screening or from historical genotype reports), an HIV-1 plasma viral load > 5000 RNA copies/mL at screening, and at least 3 documented primary protease inhibitor (PI) mutations. Patients will be randomized in a 1:1 ratio to either TMC125 (200 mg twice daily) or to matching placebo; both in combination with TMC114/RTV (600/100 mg twice daily) and an investigator selected OBR of at least 2 antiretrovirals (ARVs), consisting of nucleoside reverse transcriptase inhibitor(s) (NRTI[s]) with or without enfuvirtide. The trial will involve a screening period of up to 6 weeks, a 48-week treatment period, and a 4-week follow-up period. Patients will take 200 mg oral doses of TMC125 tablets or placebo tablets; twice daily (administered as 2 tablets twice daily, with food) in combination with 600 mg oral doses of TMC114 tablets and 100 mg oral doses of ritonavir (administered as 2 tablets of TMC114 and 1 capsule of ritonavir twice daily, with food). The treatment period is 48 weeks.

  Eligibility

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

Inclusion Criteria:

  • Patient has 3 or more primary protease inhibitor mutations
  • documented genotypic evidence of resistance to currently available NNRTIs by having at least 1 NNRTI (non-nucleoside reverse transcriptase inhibitors) resistance-associated mutation
  • on a stable antiretroviral therapy for at least 8 weeks
  • plasma viral load at screening visit > 5000 HIV-1 RNA copies/mL.

Exclusion Criteria:

  • Active AIDS defining illnesses (except for stable, cutaneous Kaposi's Sarcoma or wasting syndrome)
  • Any grade 3 or grade 4 toxicity according to the DAIDS grading scale
  • Use of disallowed concurrent therapy
  • Any active clinically significant disease
  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: NCT00254046

  Show 56 Study Locations
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00254046     History of Changes
Other Study ID Numbers: CR002752, TMC125-C206
Study First Received: November 10, 2005
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
HIV
HIV-1
TMC125

Additional relevant MeSH terms:
Etravirine
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014