E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Each subject must be 18 years of age with a diagnosis of HIV Infections |
Soggetti adulti di età ≥18 anni affetti da HIV (Virus dell’immunodeficienza umana) |
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E.1.1.1 | Medical condition in easily understood language |
Subjects with a diagnosis of HIV infection. |
Adulti affetti da HIV |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 assess the changes in renal function (e.g. estimated GFR measured by MDRD formula with 6 variables
that is MDRD 4 variables plus blood urea nitrogen and albumin) and the frequency of experiencing a
decline of renal function in HIV-infected patients with an eGFR (MDRD-6 variables) < 60 mL/ min/1.73 m2
at 48 weeks of follow up. |
Valutare i cambiamenti nella funzionalità renale (ad esempio, GFR stimato misurato con la formula MDRD a 6 variabili che è caratterizzata da MDRD a 4 variabili più concentrazione di azoto ureico e albumina nel sangue) e la frequenza di un peggioramento della funzionalità renale nei pazienti con infezione da HIV con un eGFR (con formula MDRD a 6 variabili) <60 ml/min/1,73 m2 alla 48ma settimana. |
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E.2.2 | Secondary objectives of the trial |
To evaluate changes in eGDR-MDRD during 96 weeks of follow up.
To assess the efficacy (stable suppressed HIV-RNA <50c/ml) after switch from PI/r (LPV/r, ATV/r, DAR/r)+TDF/FTC to RAL + NVP + 3TC in patients with a stable HIV-1 RNA < 50 copies/mL in the previous 12months during 48 and 96 weeks.
To assess laboratory alterations (liver enzymes, lipid profile) after switch from PI/r (LPV/r, ATV/r, DAR/r) +
TDF/FTC to RAL + NVP + 3TC in patients with a stable HIV-1 RNA < 50 copies/mL in the previous 12
months during 48 and 96 weeks |
1. Valutare le variazioni nell’eGDR-MDRD nel corso di 96 settimane di trattamento.
2.Valutare l’efficacia alla settimana 48 e 96 (viremia HIV-RNA soppressa stabile <50 c/ml) dopo il passaggio dal regime Pl/r (LPV/r, ATVIr, DARIr) + TDF/FTC al regime RAL + NVP + 3TC in pazienti con HIV-1 RNA stabile <50 copie/ml nei 12 mesi precedenti al cambio di regime.
3.Valutare le alterazioni nei valori di laboratorio, alla settimana 48 e 96, (enzimi epatici, profilo lipidico) dopo il passaggio dal regime Pl/r (LPV/r, ATV/r, DAR/r) + TDF/FTC a RAL + NVP + 3TC in pazienti con HIV-1 RNA stabile <50 copie/ml nei 12 mesi precedenti al cambio di regime.
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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 |
PK Substudy (Pharmacocinetic Substudy),MK-0518-284 -01 Amendment dated 17 Dec 2013 |
Sottostudio di farmacocinetica,MK-0518-284 -01 Amendment dated 17 Dec 2013 |
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E.3 | Principal inclusion criteria |
1. Each subject must be 18 years of age.
2. Each subject must be male or non-pregnant, non-breastfeeding female
3. Each subject must have diagnosis of HIV infection.
4. Each subject must have no history of previous virological failure (defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL while on previous or current ARV therapy)
5. Each subject must have no history of previous exposure to NNRTIs or INIs prior to entering the study
6. Each subject must have no history of previous intolerance to Lamivudine
7. Each subject must have at least 2 documented plasma HIV-1 RNA <50 copies/mL and no HIV-1 RNA >50 copies/mL in the 12 months prior to the screening visit
8. Each subject must be taking the same PI/r + TDF/FTC based ARV combination for at least 6 months before screening
9. Each subject mustn't have major IAS-USA mutations on genotypic testing performed before starting ARV treatment. |
1.Ogni soggetto deve avere un’età pari o superiore a 18 anni.
2. Ogni soggetto deve essere di sesso maschile o, se di sesso femminile, non deve essere in gravidanza o in allattamento.
3.Ogni soggetto deve avere una diagnosi di infezione da HIV.
4.Ogni soggetto non deve avere nessuna storia di pregresso fallimento virologico (definito come 2 analisi consecutive con livelli plasmatici di HIV-1 RNA >200 copie/ml, durante la precedente o attuale terapia ARV).
5.Ogni soggetto non deve avere nessuna storia di pregressa esposizione a NNRTl o INl prima di entrare nello studio.
6.Ogni soggetto non deve avere nessuna storia di pregressa intolleranza alla Lamivudina.
7.Ogni soggetto deve avere almeno 2 analisi documentate con livelli plasmatici di HIV-1 RNA <50 copie/ml e nessuna evidenza di HIV-1 RNA >50 copie/ml nei 12 mesi precedenti alla visita di screening.
8.Ogni soggetto deve assumere la stessa combinazione ARV con Pl/r + TDF/FTC per almeno 6 mesi prima dello screening.
9.Ogni soggetto non deve avere mutazioni maggiori IAS-USA sul test genotipico eseguito prima di iniziare la terapia ARV.
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E.4 | Principal exclusion criteria |
1.The subject has HBsAg+ or anticipated need for HCV-treatment
2. The subject has grade 2-4 laboratory abnormality of liver transaminases (ALT and AST)
3. The subject has experiencing liver cirrhosis
4. The subject has an allergy/sensitivity to investigational product or its/their excipients.
5. The female subject is nursing.
6. The female subject is pregnant or intending to become pregnant.
7. The subject has any clinically significant condition or situation, other than the condition being studied that,
in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the
trial.
8. The subject has active AIDS-defining event (CDC-C), exception for stable Kaposi Sarcoma, HIV Wasting
Syndrome. |
1.Il soggetto è HBsAg+ o si prevede che necessiterà di trattamento per HCV
2.Il soggetto presenta un’anomalia di laboratorio di grado 2-4 delle transaminasi epatiche (ALT e AST)
3.Il soggetto soffre di cirrosi epatica
4.Il soggetto è allergico/sensibile al prodotto sperimentale o ai rispettivi eccipienti.
5.Il soggetto di sesso femminile sta allattando.
6.Il soggetto di sesso femminile è in gravidanza o intende intraprendere una gravidanza.
7.Il soggetto ha una condizione o una situazione clinicamente significativa, diversa dalla condizione oggetto di studio che, a giudizio dello sperimentatore, potrebbe interferire con le valutazioni della sperimentazione o con una partecipazione ottimale alla sperimentazione.
8.Il soggetto presenta un evento attivo che definisce l’AIDS (CDC-C), fatta eccezione per il sarcoma di Kaposi stabile e della sindrome da deperimento da HIV.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point will be the change from BL in eGFR (MDRD) at Week 48. |
L’endpoint primario dello studio sarà il cambiamento tra il BL e la settimana 48 dell’ eGFR (MDRD). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The detection time is between baseline and week 48 |
Il tempo di rilevazione è compreso tra il basale e la settimana 48. |
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E.5.2 | Secondary end point(s) |
The Main Secondary Efficacy End-point will be the proportion of subjects with HIV-RNA < 50 cp/ml at 48 weeks according to intent-to-treat (ITT) analysis. |
L’endpoint secondario di efficacia principale sarà la percentuale di soggetti con HIV-RNA < 50 cp/ml alla settimana 48 in base all’analisi di Intent to Treat (ITT). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The detection time is between baseline and week 48 |
Il tempo di rilevazione è compreso tra il basale e la settimana 48. |
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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 | No |
E.6.5 | Efficacy | No |
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 | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
regime terapeutico a base di PI/r ovvero Inibitore della Proteasi boosted (Lopinavir-boosted OPPURE |
regimen consisting of PI / r or boosted protease inhibitor (lopinavir-boosted atazanavir-boosted OR |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 15 |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |