An Open Label Trial of TMC114/RTV in HIV-1 Infected, Treatment-experienced Subjects.

Study Overview
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Brief Summary
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The primary objective of the TMC114-C215 study is to evaluate the safety and tolerability of TMC114/RTV over time. The secondary objectives are to evaluate the antiviral activity over time and to evaluate the immunological effect over time.

Detailed Description
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The study will continue for 144 weeks after study medication has begun. For patients failing treatment, they must have participated in the TMC114-C213 or TMC114-C202 for at least 12 weeks and meet specific virologic failure criteria. It is estimated that approximately 150 patients may meet these criteria. Major inclusion and exclusion criteria are listed below. For new patients, they must have been on prior antiretroviral therapy, including more than one nucleoside reverse transcriptase inhibitor (NRTI), one non-nucleoside reverse transcriptase inhibitor (NNRTI) and a protease inhibitor (PI). At least one primary PI mutation must be present at screening. Many of the same centers that are participating in the TMC114-C213 and TMC-114 -C202 studies are also participating in the TMC114-C215 study. All sites have the chance to recruit rollover patients into the TMC114-C215 study and some sites listed had approval to recruit new patients into the study. The recruitment of new patients for the TMC114-C215 trial has been fully enrolled. The TMC114-C202 and TMC114-C213 have completed so no more patients are enrolled in this study. Two 300mg/100mg Darunavir/Ritonavir tablets twice daily for 144 weeks.

Official Title
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An Open Label Trial of TMC114/RTV in HIV-1 Infected, Treatment-experienced Subjects.

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: TMC114


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous participation in the TMC114-C202 or TMC114-C213 trials Significant virologic failure during participation in the above trials Study participation in the treatment phase of the original trial for a total of at least 12 weeks before TMC114-C215 screening Patient agrees to take TMC114/RTV with at least 2 other antiretrovirals (NRTIs), with or without T-20, from baseline onwards Patient has given informed consent Exclusion Criteria: Use of disallowed concomitant therapy Patient with clinical or laboratory evidence of active liver disease, liver impairment/ dysfunction or cirrhosis irrespective of liver enzyme levels Any active or unstable medical condition that, in the investigator's opinion, would compromise the subject's safety Patient with laboratory abnormalities at screening as defined by ACTG grading scheme as listed in the protocol Patient withdrawing consent from TMC114-C202 or TMC114-C213

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>TMC114600/100 mg tablets of TMC114/rtv BID for 144 weeks or until commercial available | Drug: TMC114<br>* 600/100 mg tablets of TMC114/rtv BID for 144 weeks or until commercial available<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary parameter is the confirmed virologic response at Week 24 (a drop in viral load (copies/mL) of at least 1 log10 versus baseline. |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a virologic response; with plasma HIV-1 RNA levels < 50 copies/mL; with plasma HIV-1 RNA levels < 400 copies/mL; Time to loss of virologic response over 144 week treatment period; Change in plasma viral load at all time points |  | 144 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMC114-C215, Ritonavir, HIV infections, TMC114-C202, TMC114-C213