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TMC114-C211: Trial of an Investigational Protease Inhibitor TMC114 With Ritonavir ("TMC114/r") in HIV-1 Infected Patients Who Have Never Been Treated With Antiretroviral Medications.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00258557
First received: November 22, 2005
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to compare the efficacy, safety and tolerability of TMC114/r versus Kaletra (a combination pill of lopinavir and ritonavir, ("lpv/rtv") in HIV-1 infected patients who have never been treated with anti-retroviral medications (referred to as "treatment-naïve" patients).


Condition Intervention Phase
HIV
Drug: LPV/RTV
Drug: TMC-114/RTV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized, Controlled, Open-label Trial to Investigate the Antiviral Activity, Tolerability and Safety of TMC114/r in Treatment- Naive HIV-1 Infected Patients.

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment [ Time Frame: 192 weeks ] [ Designated as safety issue: No ]

Enrollment: 692
Study Start Date: September 2005
Study Completion Date: May 2012
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 002
TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks
Drug: TMC-114/RTV
two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks
Active Comparator: 001
LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks
Drug: LPV/RTV
400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks

Detailed Description:

This is a randomized, controlled, open-label trial to investigate the antiviral activity, tolerability and safety of TMC114/r) versus lpv/rtv in treatment-naive HIV-1 infected patients. Six hundred sixty treatment-naïve HIV-1 infected patients will be randomized in a 1:1 ratio to either 800/100 mg of TMC114/r once daily, or a total daily dose of 800/200 mg of lpv/rtv. All patients will take TMC114/r or lpv/rtv in combination with an NRTI background of Truvada (a combination pill of tenofovir and emtricitabine, "TDF/FTC"). The trial will consist of a screening period of approximately 14 to 28 days and a 96-week treatment period, followed by a 4-week follow-up period. The anti HIV-1 therapy initiated at baseline cannot be changed until the end of the treatment period. After the end of the treatment period (maximum of 96 weeks), patients will be followed for an additional 4 weeks to follow-up on any adverse events or laboratory abnormalities until resolution. Patients who fail either virologically or due to intolerance from the TMC114/r or lpv/rtv therapy, as judged by the investigator, or who meet one of the withdrawal criteria will be withdrawn from the trial and may have the opportunity to participate in the rollover phase of the trial.

The primary efficacy parameter is virologic response defined as a confirmed viral load < 50 copies/mL at Week 48 the objective of this study is to establish non-inferiority of TMC114/r versus lpv/rtv in terms of virologic response at Week 48 using a non-inferiority margin of 12%. To test this hypothesis, a two-sided 95% confidence interval (CI) of the difference in response rate between TMC114/r and lpv/rtv will be derived: If the lower bound of the CI exceeds -12%, non-inferiority will be concluded. Patients will take oral doses for up to 96 weeks of either 800/100mg of TMC114/r 1x/day or 800/200mg of lpv/rtv once daily, each in combination with TDF/FTC. (The 400/100 mg 2x/day dose of lpv/rtv will be used where the 1x/day use of lpv/rtv is not approved).

  Eligibility

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

Inclusion Criteria:

  • Patients with documented HIV-1 infection
  • Screening plasma HIV-1 RNA >= 5000 copies/mL
  • Patients qualify for treatment initiation based on the investigator's assessments and/or according to treatment guidelines
  • Patients who can comply with the protocol requirements
  • General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial.

Exclusion Criteria:

  • Presence of any currently active AIDS defining illness or receiving treatment for primary HIV infection
  • Life expectancy of less than 6 months
  • Previous or current use of antiretroviral medications (ARVs) for the treatment of HIV-infection or hepatitis B infection with anti-HIV activity
  • Female -patients who are pregnant or breast-feeding, or are of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period
  • -patients with a grade 3 or 4 laboratory abnormality as defined by DAIDS grading, or a calculated creatinine clearance (CLCr) < 70 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: NCT00258557

  Show 93 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: NCT00258557     History of Changes
Other Study ID Numbers: CR002800, TMC114-C211
Study First Received: November 22, 2005
Last Updated: June 25, 2013
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
HIV
Anti-Retroviral agents
HIV-1
TMC114/r
Treatment naïve patients
Anti-Retroviral Agents

Additional relevant MeSH terms:
Anti-Retroviral Agents
Darunavir
Anti-HIV Agents
Anti-Infective Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014