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.

Study Overview
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Brief Summary
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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).

Detailed Description
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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from the TMC114/r or lpv/rtv therapy, as judged by the investigator, or who meet one of the withdrawal criteria will be withdrawn from the trial and may have the opportunity to participate in the rollover phase of the trial.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).

Official Title
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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.

Conditions
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HIV

Intervention / Treatment
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* Drug: LPV/RTV
* Drug: TMC-114/RTV


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 002<br>TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks | Drug: TMC-114/RTV<br>* two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks<br>|
| Active Comparator: 001<br>LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks | Drug: LPV/RTV<br>* 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48 |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment |  | 192 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Anti-Retroviral agents, HIV-1, TMC114/r, Treatment naïve patients