Clinical trial NCT00354627: The TMC125-C214 Study Provides Early Access to TMC125 for HIV-1 Infected Patients Who Have Failed Multiple Antiretroviral Regimens and Will Also Gather Information on the Long-term Safety and Tolerability of TMC125 Combined With Other Antiretroviral Drugs
Official title: Early Access of TMC125 in Combination With Other Antiretrovirals in Treatment-experienced HIV-1 Infected Subjects With Limited Treatment Options
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1
Keywords: HIV-1
Early Access Program (EAP)
TMC125
treatment-experienced
failing multiple antiretroviral (ARV) regimens
limited to no treatment options
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2006-07-20
Enrollment: 5178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to provide early access of TMC125 to HIV-1 infected patients who have failed multiple antiretroviral (ARV) regimens. Information on safety and tolerability aspects of TMC125 in combination with other ARVs in treatment-experienced HIV-1 patients with limited treatment options will be assessed. Available data regarding the effectiveness of the drug will also be collected. To be eligible, patients should be failing their current ARV regimen or be on a treatment interruption, should have previously received 2 different protease inhibitor (PI) containing regimens and be at least 3-class experienced (protease inhibitors \[PI\], nucleoside/tide reverse transcriptase inhibitors \[N\[t\]RTIs\] and non-nucleoside reverse transcriptase inhibitors \[NNRTIs\]) or at least 2-class experienced (PIs and N\[t\]RTIs) with primary NNRTI resistance. TMC125 will be administered in combination with an investigator-selected background of additional ARVs from the list of allowed medications.

Detailed description: This is an open label trial with primary objective to provide early access to TMC125 for treatment-experienced HIV-1 infected patients who have failed multiple antiretroviral (ARV) regimens and have limited treatment options with currently approved ARVs. The secondary objective of this trial is to gather information on the safety and tolerability aspects of TMC125 in combination with other ARVs. Available efficacy data will also be collected. Patients should be at least 3-class experienced or 2-class experienced with primary non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. They should also have previously received 2 different protease inhibitor-based regimens (low-dose ritonavir is not counted as a protease inhibitor (PI) regimen), be on a treatment interruption or not be virologically suppressed on their current regimen, and not be able to use currently approved NNRTIs due to resistance (primary or acquired) and/or intolerance. Patients must also meet all in- and exclusion criteria. TMC125 (200mg twice daily) will be provided once the patient has been confirmed eligible for entry. Once treatment with TMC125 in combination with other ARVs has been initiated, patients must be instructed to follow the recommended visit schedule based on routine clinical care. Safety and tolerability of the entire antiretroviral therapy (ART) regimen, including TMC125, should be monitored by the investigator as per standard clinical practice. However, it is recommended that visits be planned 4 and 12 weeks following initiation of TMC125 in combination with other ARVs and every 12 weeks thereafter while on therapy during this trial. Adverse events (AEs) leading to treatment interruption or discontinuation and all serious adverse events (SAEs), with the exception of Acquired Immunodeficiency Syndrome (AIDS) defining illnesses (CDC class C) unless fatal or considered to be related to TMC125, will be collected. Other adverse events will be collected only if required as per local regulations. The background ARVs may be changed at any time during the trial, at the discretion of the investigator due to the development of resistance, intolerance, toxicity, etc. while continuing treatment with TMC125 if in the investigator's assessment the patient still benefits from treatment with TMC125. If changes in the background regimen are made, it is recommended that a follow-up visit be planned 4 weeks after the change in therapy. Treatment with investigational medication will be continued until virologic failure, treatment-limiting toxicity, subject lost to follow-up, patient's withdrawal, pregnancy, discontinuation of TMC125 development or when TMC125 has become commercially available in the patient's country. Patients will be instructed to orally take two 100 mg tablets of TMC125 following a meal every 12 hours. TMC125 (200 mg twice daily) must be used in combination with other antiretroviral drugs. Treatment with investigational medication will continue until virologic failure, treatment-limiting toxicity, patient lost to follow-up, withdrawal, pregnancy, discontinuation of TMC125 development or when TMC125 becomes commercially available in the patient's country.

Eligibility criteria: Inclusion Criteria:

* Patient is at least 3-class experienced (3 classes of licensed oral antiretrovirals: nucleoside/tide reverse transcriptase inhibitors \[N\[t\]RTI\], protease inhibitors \[PI\], non-nucleoside reverse transcriptase inhibitors \[NNRTI\])
* Patients with primary NNRTI resistance can be included if they are experienced with at least 2 classes of ARVs (PIs, N\[t\]RTIs) and meet all the other inclusion criteria
* Patient has previously received 2 different PI-based regimens
* Patient is unable to use currently approved NNRTIs due to resistance (primary or acquired) and/or intolerance
* Patient, if currently receiving an ARV regimen, is not achieving adequate virologic suppression on his/her current regimen.

Exclusion Criteria:

* Prior or current participation in DUET trials (TMC125-C206 or TMC125-C216).
* Use of disallowed concomitant therapy, including disallowed antiretrovirals (ARV)
* Use of investigational ARVs (with exceptions)
* Any active clinically significant disease (e.g., cardiac dysfunction, pancreatitis, acute viral infection) or findings during screening of medical history or physical examination that is not either resolved or stabilized for at least 30 days before the Screening Phase
* Pregnant or breast-feeding female
* Female patient of childbearing potential not using effective non-hormonal birth control methods
* Patients with specific laboratory abnormalities
* Patients with clinical or laboratory evidence of significantly decreased hepatic function or decompensation.

Primary outcomes:
measure: The primary objective of TMC125-C214 is to provide early access to TMC125 for treatment-experienced HIV-1 infected patients who have failed multiple antiretroviral (ARV) regimens and have limited treatment options with currently approved ARVs.
timeFrame: pregnancy, discontinuation of TMC125 development or when TMC125 has become commercially available in the patient's country.
Secondary outcomes:
measure: The secondary objective of this trial is to gather information on the safety and tolerability aspects of TMC125 in combination with other ARVs. Available efficacy data will also be collected.
timeFrame: pregnancy, discontinuation of TMC125 development or when TMC125 has become commercially available in the patient's country.
Other outcomes:
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country: Germany
city: Athens
country: Greece
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country: Netherlands
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country: Netherlands
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country: Netherlands
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country: Netherlands
city: Utrecht
country: Netherlands
city: San Juan
country: Puerto Rico
city: Moscow N/A
country: Russian Federation
city: Moscow
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Alicante
country: Spain
city: Barcelona N/A
country: Spain
city: Barcelona
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country: Spain
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country: Spain
city: Cuenca
country: Spain
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city: Granada
country: Spain
city: Granollers
country: Spain
city: La Laguna
country: Spain
city: Logrono
country: Spain
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country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Murcia
country: Spain
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country: Spain
city: Oviedo
country: Spain
city: Sabadell
country: Spain
city: Santiago De Compostela (La Cor
country: Spain
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country: Spain
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country: Spain
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country: Spain
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country: Spain
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city: Valencia
country: Spain
city: Vigo
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city: Vitoria-Gasteiz
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city: Göteborg
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
city: Kaohsiung City
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taipei
country: Taiwan
city: Ankara
country: Turkey
Study officials:
affiliation: Tibotec Pharmaceutical Limited
name: Tibotec Pharmaceuticals Clinical Trial
role: STUDY_DIRECTOR
References: