A Trial With TMC278-TIDP6-C222 for Continued TMC278 Access in Patients Infected With Human Immunodeficiency Virus-1

Study Overview
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Brief Summary
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The purpose of the study is to provide continued access to TMC278 in HIV-1 infected patients who were randomized and treated with TMC278 in the Phase IIb or Phase III trials.

Detailed Description
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This is a Phase III, open-label (all people know the identity of the drug), multicenter, roll-over trial to provide continued access to TMC278 to HIV-1 infected patients who were randomized (the study drug is assigned by chance) and treated with TMC278 in the Phase IIb (TMC278-C204 [C204]) or Phase III trials (i.e., TMC278-TiDP6-C209 [C209] or TMC278-TiDP6-C215 [C215]) and who continue to benefit from their antiretroviral treatment, according to the investigator. In addition, information on the long-term safety and tolerability, including resistance data in case of virologic failures, of oral doses of TMC278 25 mg once daily (q.d.) in combination with a background regimen containing 2 N(t)RTIs will be collected. Available efficacy data will also be collected. Approximately 750 HIV-1 infected individuals are expected to participate in this trial. The duration of participation in the study for an individual participant will be 2 to 3 years. The final/withdrawal visit of the Phase IIb or Phase III trials will be the first visit of this trial. Safety and tolerability will be evaluated throughout the trial. Visits and assessments performed should be based on the local, generally accepted standard of care, with visits occurring at least every 6 months. Oral tablets of TMC278 25 mg once daily (q.d.) should be administered together with a meal.

Official Title
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An Open-label Trial With TMC278 25 mg q.d. in Combination With a Background Regimen Containing 2 N(t)RTI's in HIV-1 Infected Subjects Who Participated in TMC278 Clinical Trials and Were Still Benefitting From Treatment With TMC278

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Rilpivirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are HIV-1 infected and were previously randomized to receive TMC278 in a TMC278 clinical trial and completed the protocol-defined treatment period. Patients continue to benefit from treatment with TMC278 in the opinion of the investigator. Patient can comply with the current protocol requirements. The patient's general medical condition, in the investigator's opinion, does not interfere with participation in the trial. Exclusion Criteria: Use of disallowed concomitant therapy. Females of childbearing potential who are pregnant, or without the use of effective birth control methods, or not willing to continue practicing these birth control methods during the trial and for at least 1 month after the end of the trial (or last intake of TMC278). Non-vasectomized heterosexually active male patients without the use of effective birth control methods or not willing to continue practicing these birth control methods during the trial and for at least 1 month after the end of the trial (or after last intake of TMC278).

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rilpivirine<br>Rilpivirine 25 mg once daily | Drug: Rilpivirine<br>* 25 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. | Up to 7 years | 
| Number of Participants With Grade 3/4 Events of Rash Irrespective of Causality | Number of participants with grade 3/4 events of rash irrespective of causality were assessed. A grade 3 rash defined as diffuse macular, maculopapular or morbilliform rash with vesicles or limited number of bullae or; rash with superficial ulcerations of mucous membranes limited to 1 anatomical site or; rash with at least one of the following: elevations in aspartate aminotransferase (AST)/alanine aminotransferase (ALT) more than 2*baseline value and at least 5 times upper limit of normal; fever greater than (>) 38 degree celsius or 100 degree fahrenheit; eosinophils > 1000/millimeter (mm)^3; serum sickness-like reaction. A grade 4 rash defined as the following: extensive or generalized bullous lesions or; Stevens-Johnsons Syndrome (SJS) or ulceration of mucous membrane involving 2 or more distinct mucosal sites or toxic epidermal necrolysis. | Up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Virologic Rebound | Time to virologic rebound was time to (first) human immunodeficiency virus type1 (HIV-1) ribonucleic acid (RNA) greater than or equal to (>=) 50 or >=200 copies/milliliter (copies/mL). The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. | Up to Week 360 | 
| Time To Treatment Failure | Time to treatment failure was defined as time to virologic rebound (time to first HIV-1 RNA >= 50 or >= 200 copies/mL) or discontinuation for reason other than RPV having become commercially available in the participating country, whichever came first, calculated as the time (in days) from baseline until treatment failure. The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. | Up to Week 360 | 
| Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Observed Case Approach Until Week 336 | The immunologic assessment was determined by change from baseline in CD4+ cell count for observed case approach. | Baseline up to weeks 96, 192, 288, 336 | 
| Change From Baseline in CD4+ Cell Count for Non-Completer Equals Failure (NC=F) Approach Until Week 336 | Change from baseline in CD4+ cell count were reported for NC=F approach (participants who discontinued because RPV became commercially available or could be accessed through another source or because the participants switched to other local [RPV-based] treatment options or local standard of care, were censored at that time; other participants after discontinuation had their CD4+ values imputed with baseline value. Intermittently missing values were imputed with a last observation carried-forward approach). | Baseline up to weeks 96, 192, 288, 336 | 
| Number of Participants With Serious Adverse Events (SAEs) | A SAE is any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect. | Up to 7 years | 
| Number of Participants With AEs Related to Rilpivirine (RPV) | Number of participants with AEs related to RPV were assessed. An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. | Up to 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1 Infection, HIV-1, HIV, TMC278-TiDP6-C222, TMC278-C222, TMC278, Rilpivirine