An Open-label Trial With TMC125 in Patients Who Have Virologically Failed in a DUET Trial (TMC125-C206 or TMC125-C216).

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the long-term safety and tolerability of TMC125 200 mg twice daily as part of an antiretroviral therapy including TMC114/rtv and an investigator selected optimized background in HIV-1 infected patients who have participated in a DUET trial (TMC125-C206 or TMC125 C216) and have met the definition of virologic failure at Week 24 or later in these trials.

Detailed Description
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This is a Phase III open-label, roll-over trial to evaluate the long term tolerability, safety, antiviral and immunological effect of TMC125 as part of an individually optimized antiretroviral therapy including TMC114/rtv in HIV-1 infected patients who participated in one of the DUET (TMC125-C206 or TMC125-C216) trials. Also the change in HIV-1 resistance over time will be evaluated. This trial offers patients meeting the definition of virologic failure at Week 24 or beyond the option to roll-over to an open-label trial where they will receive TMC125 and TMC114/rtv. Three hundred patients are estimated to enroll into this trial. The withdrawal visit of the DUET trial will be the first visit of this trial. From this visit onward, all patients will receive 200 mg twice daily TMC125 and 600/100 mg twice daily TMC114/rtv until both TMC114 and TMC125 are commercially available or the therapy is no longer of clinical benefit to the patient. Patients will receive an antiretroviral therapy consisting of TMC125 as the only non-nucleoside reverse transcriptase inhibitor (NNRTI), TMC114/rtv as the only protease inhibitor (PI) and an optimized background, which will be selected by the investigator according to the local standard of care, the patient's experience with previous therapies and most recent resistance testing. The most recent HIV-1 genotype-analysis system report results from the DUET trial will be made available. TMC125 will be dosed at 200 mg twice daily, administered orally as 2 tablets twice daily with food.TMC114/rtv will be dosed at 600/100 mg twice daily, administered orally as 2 tablets TMC114 and 1 capsule ritonavir twice daily with food.The optimized background will comprise of at least 1 approved ARV drug: 1 or more NRTI(s), with or without ENF. Administration will continue until both TMC114 and TMC125 are commercially available or therapy is no longer of clinical benefit to the patient.

Official Title
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An Open-label Trial With TMC125 as Part of an ART Including TMC114/Rtv and an Investigator-selected OBR in HIV-1 Infected Subjects Who Participated in a DUET Phase III Trial (TMC125-C206 or TMC125-C216).

Conditions
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HIV-1

Intervention / Treatment
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* Drug: TMC125


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient was previously randomized in a DUET (TMC125-C206 or TMC125-C216) trial and completed at least 24 weeks of treatment Patient was virologically failing in a DUET trial. Exclusion Criteria: Use of disallowed concomitant therapy Any grade 4 toxicity according to the Division of AIDS (DAIDS) grading table Patients who had to be withdrawn from the DUET (TMC125-C206 or TMC125-C216) trials because of any of the mandatory withdrawal criteria of that trial.

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>TMC125 200 mg twice daily until commercially available | Drug: TMC125<br>* 200 mg twice daily until commercially available<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Experiencing Adverse Events | The table below provides the number of participants who experienced Serious Adverse Events (SAEs) and Other Adverse Events (except SAEs) that started or worsened in severity during the overall TMC125-C217 treatment period. The duration of treatment ranged per patient from 1 week to 180 weeks, with a median of 62 weeks. | 1 week to 180 weeks, with a median of 62 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Virologic Outcomes Over Time | The table below shows the percentage of participants with virologic suppression (< 50 copies/mL), the percentage of participants who were virologic failures (VF) (>50 copies/mL, discontinued prior to time X for reasons of VF or for other reasons, except for VF or adverse event, with a last viral load >50 copies/mL), and the percentage of participants with no viral load (VL) data available over time (ie, at Weeks 24, 48, and 96). | Weeks 24, 48, and 96 | 
| Change in Plasma Viral Load Versus Baseline (ie, Mean Change in log10 Plasma Viral Load From Baseline Over Time) | In the table below, the total number of participants analyzed in the Duet Placebo and Duet TMC125 groups, respectively at each time point were: Baseline (256;247 participants), Week 24 (251;240 participants), Week 48 (235;192 participants), and Week 96 (123;69 participants). | Baseline, Week 24, Week 48, and Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, treatment experienced, virologic failure