E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infected patients co-infected with HCV or HBV with a minimum of 3-months duration for each class and have documented resistance to more than one PI. |
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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 | HLT |
E.1.2 | Classification code | 10052740 |
E.1.2 | Term | Acquired immunodeficiency syndromes |
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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 objective of this study is to assess the safety and efficacy of TPV/r 500 mg/200 mg BID in ARV therapy experienced HIV-1 infected patients co-infected with HCV or HBV in the presence of an NRTI-based, resistance-driven optimized background regimen |
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E.2.2 | Secondary objectives of the trial |
The objective of the TDM pilot evaluation is to determine the potential utility of therapeutic drug monitoring in the use of TPV/r in co-infected patients. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
-HIV-1 infected males or females 18 years of age. -Three-class NRTI, NNRTI, and PI treatment-experienced a minimum of 3-months duration for each class with resistance to more than one PI on the screening resistance testing . -Chronic hepatitis C Virus infection demonstrated by HCV-RNA positivity or, Chronic hepatitis B infection demonstrated by anti-HBc-IgG Antibody and HB Surface Antigen positivity. -CD4 T lymphocyte count 50 cells/mm 3. -HIV-1 VL 1000 copies/mL at screening. -Patients must have at least one of the following permutations of active ARV medications available and must be willing to use them in the OBR for trial inclusion -Two genotypically active RTIs defined as two drugs that are reported as sensitive in the genotype report. -One genotypically active RTI reported as sensitive in the genotype report and Enfuvirtide ENF if not used previously. For patients who had previously taken 3TC Lamivudine or FTC Emtricitabine , these drugs are not considered as sensitive regardless of genotype report. -Only the four AIDS defining events listed below are acceptable as long as the event has been cured for at least 2 weeks before screening Visit 1 . Patients with history of other AIDS defining events are not allowed into the trial. The acceptable prior AIDS defining events include Candidiasis bronchi, trachea, lungs, esophageal , Herpes simplex chronic ulcer s 1 month s duration , bronchitis, pneumonitis, or esophagitis, Mycobacterium tuberculosis pulmonary or extrapulmonary , Pneumonia including Pneumocystis jiroveci formerly carinii pneumonia. |
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E.4 | Principal exclusion criteria |
-ARV medication na ve. -Genotypic resistance to TPV defined as a TPV mutation score 7 . -Decompensated liver disease, including presence or history of ascites, variceal bleeding, or hepatic encephalopathy or having ever been diagnosed as having hepatic insufficiency of Child Pugh class B or C. -Use of immunomodulatory drugs e.g., interferon, cyclosporin, hydroxyurea, interleukin 2 or antineoplastic agents within 30 days before study entry or during the trial. -Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the month prior to screening. -Female patients of child-bearing potential who a. have a positive serum pregnancy test at screening or during the study, b. are breast feeding, c. are planning to become pregnant, d. are not willing to use a barrier method of contraception, or e. are only willing to use an estrogen-containing medication, e.g., ethinyl estradiol, as a method of contraception. -Prior tipranavir use -Anticipated need for any interferon-based regimen in the 48 weeks following the study entry -Inability to adhere to the requirements of the protocol, including active substance abuse, as defined by the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
is treatment response at Week 48. Treatment response is a confirmed virologic response, defined as a viral load 50 copies/mL at two consecutive measurements at least 5 days apart, without, death, permanent discontinuation of the study drug or loss to follow-up, or introduction of a new antiretroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background drug . The Primary safety endpoint is the occurrence of dose-limiting hepatotoxicity during the study. Dose-limiting hepatotoxicity is defined as Grade 4 ALT or AST elevation confirmed in 48h or any evocative symptoms or signs of hepatitis, if it not clearly attributable to another cause. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |