E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is to provide early access to TMC125 for treatment-experienced HIV-1 infected subjects who have failed multiple ARV regimens and have limited treatment options with currently approved ARVs. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects who meet all of the following criteria are eligible for this trial. 1. Subject or Legal Authorized Representative has voluntarily given informed consent before initiation of trial procedures. 2. Subject has documented HIV-1 infection. 3. Male or female subject over 18 years of age. 4. Subject has limited treatment options due to virological failure or intolerance to multiple ARV regimens. 5. Subject is at least 3-class experienced (3 classes of licensed oral ARVs: N[t]RTIs, PIs, NNRTIs). Note: Subjects 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. 6. Subject has previously received 2 different PI-based regimens. 7. Subject is unable to use currently approved NNRTIs due to resistance (primary or acquired) and/or intolerance. 8. Subject, if currently receiving an ARV regimen, is not achieving adequate virologic suppression on his/her current regimen (defined as a confirmed detectable plasma VL on the current treatment). |
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E.4 | Principal exclusion criteria |
Subjects meeting one or more of the following criteria cannot be selected. 1. Primary HIV infection. 2. Prior or current participation in DUET trials (TMC125-C206 or TMC125-C216). 3. Any condition (including but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the subjectメs safety or adherence to the protocol. 4. Use of disallowed concomitant therapy, including disallowed ARVs (See Section 5.3.8.2). 5.Use of non-ARV investigational medications within the 30 days prior to baseline visit. 6. Use of investigational ARVs, unless stated as an exception in Section 5.3.8.2.2. 7. 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 of the trial. 8. Acute viral hepatitis, including but not restricted to A, B or C. 9. Pregnant or breast-feeding female. 10. Female subject of childbearing potential not using effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until the last trial related activity. 11. Subjects with the following laboratory abnormalities as defined by a standardized grading scheme based on the Division of AIDS (DAIDS) grading table (updated version from December 2004, see Section 7.2): - Hemoglobin < 7.4 g/dL (4.5 mmol/L) - Absolute neutrophil count < 500/mmᄈ (0.500 x 109/L) - Platelets <25,000/mm3 (25.000 x 109/L) - Prothrombin time (PT) >1.50 x upper limit of laboratory normal range (ULN) Note: Subjects on anticoagulant therapy with elevated PT >1.5 ULN require approval of the sponsor prior to enrollment. - Alkaline phosphatase >5 x ULN - Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) >5 x ULN Bilirubin > 5 x ULN Note: Subjects with elevated bilirubin >5xULN assessed as related to a component of ART therapy may be enrolled with prior approval of the sponsor. - Lipase >3 x ULN - Amylase >5 x ULN if lipase >2 x ULN - Creatinine >1.8 x ULN 12. Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels. 13.Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (TMC125). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The trial is not set up to show a specific statistical hypothesis but to provide TMC125 to ARV experienced HIV-1 infected subjects with limited treatment options. Further objective is to gather information on safety and tolerability aspects of TMC125. Safety of TMC125 will be summarized in terms of -mortality -non-HIV related SAEs -subject's disposition. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |