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 | 10064446 |
E.1.2 | Term | HIV infection WHO clinical stage I |
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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 |
To compare the antiretroviral efficacy of ATC to lamivudine (3TC) in treatment experienced, HIV-1 infected patients with the M184V/I mutation in reverse transcriptase To compare the safety and tolerability of ATC to lamivudine (3TC) in treatment experienced, HIV-1 infected patients |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of ATC vs. 3TC upon CD4+ and CD8+ T-cell counts To investigate the influence of increasing nucleoside associated mutations (NAMs) in reverse transcriptase upon the antiretroviral efficacy of ATC To investigate the emergence of ATC-associated HIV-1 resistance mutations |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
HIV-1 positive with M184V/I mutation in reverse transcriptase 18 years of age or older Stable ART regimen containing either lamivudine (3TC) or emtricitabine (FTC) unchanged for at least 2 months prior to baseline At least 2-class experienced Plasma HIV-1 RNA  2,000 copies/mL Unrestricted CD4+ cell count Written, informed consent |
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E.4 | Principal exclusion criteria |
HIV-2 infection Presence of Q151M or 69 insertion mutations in HIV-1 reverse transcriptase Clinically relevant current or recurring disease, illness or laboratory abnormality likely to require treatment during the study that could affect interpretation of efficacy end-points eg, HIV-1 RNA levels Female patients with a positive pregnancy test or who are breastfeeding Current active hepatitis B virus (HBV) infection, (HBsAg positive and requiring treatment within the next 12 months) o Well controlled HBV-infected patients not taking tenofovir as part of the OBR and who have been receiving adefovir dipivoxil for at least 30d prior to screening, who meet the requirements for AST and ALT < 3 times upper limit of normal range (ULN) and who continue on adefovir dipivoxil for the duration of the study may be enrolled. Adefovir dipivoxil should not be prescribed concurrently with tenofovir in this study due to concerns over potential renal toxicity. Current treatment for hepatitis C virus infection, or treatment required within the next 12 months A new AIDS-defining condition (Category C, Appendix 1) diagnosed within 42 days prior to baseline with the exception of CD4 cells <200/mm3, Kaposis sarcoma (KS) confined to the skin and HIV-wasting disease ie, wasting not related to any other known cause Patients who, within 42 days prior to baseline, have received immunomodulating agents, immunization other than for influenza or pneumococcus, systemic chemotherapeutic agents, an HIV prophylactic or immunotherapeutic vaccine Haemoglobin <10.0 g/dL for men and <9.0 g/dL for women Neutrophil count <750/mm3 Platelet count <50,000/mm3 AST or ALT ≥3 times ULN Total bilirubin is >1.5 x ULN, with the exception of patients receiving atazanavir or any other medication known to elevate the indirect bilirubin level as long as the direct bilirubin is less than the ULN. Lipase >3 times ULN Amylase >3 times ULN (unless serum lipase is  1.5 times the ULN) Estimated creatinine clearance (Cockcroft Gault) <50mL/min Patients who have previously received ATC. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Proportion of patients with plasma HIV-1 RNA <400 copies/mL at W24 |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 | Yes |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 8 |