| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV-1 infected patients who have received no previous antiretroviral treatment (of more than 7 days in total) |
| Pazienti infetti da HIV-1 che non hanno ricevuto in precedenza alcun trattamento antiretrovirale da piu' di 7 giorni |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020161 |
| E.1.2 | Term | HIV infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 efficacy and safety of RTV-boosted atazanavir with nevirapine in two different dosing schedules, each on a background of emtricitabine and tenofovir DF. |
| Valutare l'efficacia e la sicurezza del trattamento con NVP (400 mg QD e 200 mg bid) rispetto ad ATZ (300 mg QD) potenziato con RTV (100 mg QD) (ATZ/r) - tutti questi trattamenti in presenza di emtricitabina (200 mg QD) e tenofovir DF (300 mg QD) come regime di base. |
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| E.2.2 | Secondary objectives of the trial |
| • Change in fasting plasma levels of total cholesterol and in its fractions (HDLC and LDLC), the TC:HDLC ratio, in apolipoprotein A1 and B, hsCRP and total triglyceride levels from baseline to after 48, 96 and 144 weeks of treatment • Change in the estimated cardiovascular risk using the Framingham algorithm of the patients in each treatment group from baseline to after 48, 96 and 144 weeks of treatment • Change in quality of life from baseline to after 24, 48, 96 and 144 weeks of treatment • Cost-effectiveness of each treatment regimen in the time periods from baseline to after 24, 48, 96 and 144 weeks of treatment |
| •Variazione rispetto al basale dei livelli plasmatici a digiuno di colesterolo totale e delle sue frazioni (HDLC e LDLC),del rapporto CT:HDLC,dei livelli di apolipoproteina A1 e B,hsCRP e trigliceridi totali esaminati dopo 48,96 e 144 settimane di trattamento •Variazione del rischio cardiovascolare stimato dei pazienti di ciascun gruppo di trattamento dal basale a dopo 48,96 e 144 settimane di trattamento,utilizzando l'algoritmo di Framingham •Variazione della qualita' della vita dal basale a dopo 24,48,96 e 144 settimane di trattamento •Convenienza economica di ciascun regime terapeutico nei periodi di tempo dal basale a dopo 24,48,96 e 144 settimane di trattamento |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI:
Sottostudio metabolico che prevede la variazione vs basale dei seguenti endpoints: lipodistrofia, lipidi sierici, glicemia, livelli plasmatici di insulina, adinopectina e leptina
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| E.3 | Principal inclusion criteria |
| -Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation -HIV-1- infected males or females >= 18 years of age with positive serology (ELISA) confirmed by Western blot - No previous antiretroviral treatment (of more than 7 days) -Males with CD4+ counts < 400 cells/mm3 and females with CD4+ counts < 250 cells/mm3 -NVP and ATZ/r susceptibility based on HIV-1 genotypic resistance report - Adequate renal function defined as a calculated creatinine clearance (CLCr) >= 50 ml/min according to the Cockcroft-Gault formula -Karnofsky score >= 70 -Acceptable medical history, as assessed by the investigator |
| - Consenso informato firmato in conformita' alle GCP e alle prescrizioni normative locali prima della partecipazione alla sperimentazione -Uomini o donne portatori di infezione da HIV-1 di eta' >= 18 anni con sierologia positiva (ELISA) confermata da Western blot -Nessun precedente trattamento antiretrovirale (per piu' di 7 giorni) -Uomini con conta dei CD4+ < 400 cellule/mm3 e donne con conta dei CD4+ < 250 cellule/mm3 -suscettibilita' a NVP e ATZ/r basata sul referto di resistenza genotipica dell'HIV-1 -Funzionalita' renale adeguata, definita come clearance della creatinina calcolata (CLCr) >= 50 ml/min secondo la formula di Cockcroft-Gault -Punteggio di Karnofsky >=70 - Storia clinica accettabile, secondo la valutazione dello sperimentatore |
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| E.4 | Principal exclusion criteria |
| -Active drug abuse or chronic alcoholism at the investigator's discretion -Hepatic cirrhosis stage Child-Pugh B or C -Female patients of child-bearing potential who: • have a positive serum pregnancy test at screening or during the study, • are breast feeding, • are planning to become pregnant, • are not willing to use a barrier method of contraception, or are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives -Laboratory parameters > DAIDS grade 2 (triglycerides > DAIDS grade 3, total cholesterol no restriction, -Active hepatitis B or C disease, defined as HBsAg-positive or HCV-RNApositive with AST/ALT > 2.5x ULN ( > DAIDS grade 1) -Hypersensitivity to any ingredients of the test products -Have therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine) or potential competitors of renal excretion (e.g., cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir, probenecid, high-dose non-steroidal anti-inflammatory drugs (i.e., ibuprofen)) within 3 months prior to study screening or are expected to receive these during the study -Patients who are receiving other concomitant treatments which are not permitted according to protocol -Use of other investigational medications within 30 days before study entry or during the trial -Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2, chronic treatment with prednisone) -Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma -Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit -Patients who are receiving systemic treatment for malignant disease -Patients who in the opinion of the investigator are not candidates for inclusion in the study |
| -Abuso di droghe o alcolismo cronico attivi, a discrezione dello sperimentatore -Cirrosi epatica di stadio B o C secondo Child-Pugh -Pazienti di sesso femminile in eta' fertile che: •risultino positive al test sierico di gravidanza allo screening o nel corso dello studio, •allattino, •intendano pianificare una gravidanza, •non siano disposte a utilizzare un metodo contraccettivo a barriera o non siano disposte a utilizzare metodi contraccettivi diversi dai contraccettivi orali contenenti etinilestradiolo -Parametri di laboratorio > grado 2 sulla scala DAIDS (trigliceridi > grado 3 sulla scala DAIDS, colesterolo totale senza limitazioni, -Epatite B o C attiva, definita come HBsAg-positiva o HCV-RNA-positiva con AST/ALT > 2,5x LSN ( > grado 1 sulla scala DAIDS) -Ipersensibilita' ai componenti dei prodotti in prova -Pazienti in terapia con farmaci nefrotossici (p.es. aminoglicosidi, amfotericina B, vancomicina, cidofovir, foscarnet, cisplatino, pentamidina, tacrolimo, ciclosporina) o potenziali competitori dell'escrezione renale (p.es. cidofovir, aciclovir, valaciclovir, ganciclovir, valganciclovir, probenecid, farmaci antinfiammatori non steroidei ad alto dosaggio (p.es. ibuprofene) ) nei 3 mesi antecedenti lo screening per lo studio o pazienti a cui si preveda di somministrare tali trattamenti nel corso dello studio -Pazienti a cui vengano somministrati altri trattamenti concomitanti non permessiin accordo al protocollo, -Uso di altri farmaci sperimentali nei 30 giorni antecedenti l'ingresso nello studio oppure nel corso della sperimentazione -Uso di farmaci immunomodulatori nei 30 giorni antecedenti l'ingresso nello studio oppure nel corso della sperimentazione (p.es. interferone, ciclosporina, idrossiurea, interleuchina 2, trattamento cronico con prednisone) -Pazienti con leucoencefalopatia multifocale progressiva (PML), sarcoma di Kaposi (KS) viscerale e/o qualunque linfoma -Qualunque malattia AIDS-definente irrisolta, sintomatica o non stabile in trattamento da almeno 12 settimane alla visita di screening -Pazienti a cui venga somministrato un trattamento sistemico per una patologia maligna -Pazienti che, a giudizio dello sperimentatore, non siano candidati all'inclusione nello studio |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the treatment response (TR) at Week 48. TR is defined as HIV viral load of < 50 copies/ml measured at two consecutive visits prior to Week 48 and without subsequent rebound or change of ARV therapy prior to Week 48. If the VL is >= 50 copies/ml at Week 48 and this is the first sequential VL value >= 50 copies/ml following treatment response, then another measurement at least 2 weeks later is necessary to determine whether rebound has occurred. A rebound is defined by two consecutive measurements of VL >= 50 copies/ml, at least two weeks apart, after two consecutive measurements of VL < 50 copies/ml. A change of ARV therapy is either defined as: • A permanent discontinuation of study drug or its control • A change in the dose of ATZ or RTV. A change from NVP once daily to twice daily administration and vice versa is not considered failure for the primary analysis. Therefore, a patient remains a treatment responder in this case if all other criteria are fulfilled. |
| L'endpoint primario e' la risposta al trattamento (TR) alla Settimana 48. Si definisce risposta al trattamento una carica virale dell'HIV< 50 copie/ml misurata in occasione di due visite consecutive prima della Settimana 48 e in assenza di successivo rialzo di carica virale (CV) o cambiamento della terapia antiretrovirale prima della Settimana 48. Se la CV e' >= 50 copie/ml alla Settimana 48 e questo e' il primo valore sequenziale di CV >= 50 copie/ml dopo la risposta al trattamento, e' necessaria un'altra misurazione a distanza di almeno 2 settimane per stabilire se si sia verificato un rialzo. Un rialzo e' definito da due misurazioni consecutive della CV >= 50 copie/ml, a distanza di almeno due settimane, dopo due misurazioni consecutive della CV < 50 copie/ml.Si definisce cambiamento della terapia ARV: •Una sospensione permanente del farmaco dello studio o del suo controllo •Un cambiamento della dose di ATZ (atazanavir) o di RTV (ritonavir). Il passaggio da NVP in monosomministrazione giornaliera alla somministrazione due volte al giorno e viceversa non e' ritenuto un fallimento per l'analisi primaria. Pertanto, in questo caso un paziente rimane ''responder'' al trattamento se vengono soddisfatti tutti gli altri criteri. |
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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 | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 12 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 45 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 45 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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