| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects suffering from hyperuricemia and gout |
| Soggetti che soffrono di iperuricemia e gotta |
|
| E.1.1.1 | Medical condition in easily understood language |
| Subjects suffering from gout and with elevate level of uric acid in blood |
| Pazienti che soffrono di gotta ed hanno livelli elevati di acido urico nel sangue |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| 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 | 10018627 |
| E.1.2 | Term | Gout |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| 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 | 10020903 |
| E.1.2 | Term | Hyperuricaemia |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| 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 main study objective is to determine whether Febuxostat 80 mg, given once a day, is better than Allopurinol 300 mg /die considering the proportion of subjects, at visit 1, whose week 4 serum urate concentration will be below 6 mg/dL (357 µmol/L) |
| L'obiettivo principale dello studio è determinare se Febuxostat 80 mg, somministrato una volta al giorno, è migliore di Allopurinolo 300 mg/die considerando la proporzione di soggetti che, alla visita 1, cioè dopo 4 settimane di trattamento, hanno concentrazione di urato sierico inferiore a 6 mg/dL (357 µmol/L) |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate: the efficacy of Febuxostat 80 mg/die, given after a four-week treatment with Allopurinol 300 mg in lowering serum urate concentration below 6 mg/dL at visit 2 (week 8 after randomisation); the efficacy of Febuxostat 120 mg, given once a day, after four weeks treatment with Febuxostat 80 mg, versus Febuxostat 80 mg and Allopurinol 300 mg/die considering the proportion of subjects at visit 2, whose week 8 serum urate concentration will be below 6 mg/dL (357 µmol/L) and considering the proportion of subjects at visit 6, whose last 3 month (at week 16, 20 and 24) serum urate concentrations will be below 6 mg/dL (357 µmol/L); the comparison of efficacy of Febuxostat 80 and 120 mg, given once a day versus Allopurinol 300 mg/die by assessment of serum urate concentrations at each post baseline visits (V 1, 2, 3, 4, 5 and 6); effect of therapy to gout flare incidence |
| Valutare: l'efficacia di Febuxostat 80mg, somministrato dopo 4 settimane di trattamento con Allopurinolo 300mg, nel ridurre l'urato <6 mg/dL alla visita (V) 2; l'efficacia di Febuxostat 120mg, dopo 4 settimane di trattamento con Febuxostat 80mg, verso Febuxostat 80mg e Allopurinolo 300mg/die considerando la percentuale di soggetti con urato minore di 6 mg/dL alla V2, dopo 8 settimane di trattamento, e considerando alla V6 la proporzione di soggetti che negli ultimi 3 mesi (alle settimane 16, 20 e 24) avevano concentrazioni di urato <6 mg/dL;confrontare l’efficacia di Febuxostat 80 e 120 mg, somministrato una volta al verso Allopurinolo 300mg/die dalla valutazione della concentrazione di urato ad ogni visita; l’effetto della terapia nell’incidenza degli attacchi acuti gottosi |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| • Subjects of both sexes suffering from hyperuricemia who had at least one episode of gout flare in their medical history • Sign and symptoms of gout flare have to be resolved at least 48 hours before enrolment or randomisation • Male or female subjects aged ≥18 years • Subjects willing and able to give written informed consent • Meeting the preliminary criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout (26 – Appendix 1) • Serum uric acid ≥ 8.0 milligrams per decilitre (mg/dL) at baseline • Subject willing to comply with the prophylaxis treatment |
| Soggetti di entrambi i sessi che soffrono di iperuricemia e che hanno avuto almeno un attacco di gotta nella loro storia medica; segni e sintomi di attacchi acuti gottosi devono essersi risolti almeno da 48 ore prima della visita di screening; uomini e donne con ≥18 anni; soggetti in grado di fornire consenso informato scritto; soggetti che rispettano i criteri prliminari dell'associazione Americana di Reumatologia per la classificicazione dell'artrite acuta gottosa; soggetti con acido urico ≥ 8.0 mg/dL al basale; soggetti disposti ad assumere il trattamento di profilassi |
|
| E.4 | Principal exclusion criteria |
| • Serum creatinine >1.5 mg/dL or calculated creatinine clearance < 60 mL/min • Pregnancy or lactation • Clinical evidence on screening visit of Ischaemic Heart Disease and/or Congestive Heart Failure • Concurrent therapy with Losartan • Concurrent therapy with urate lowering agents, azathioprine, 6-mercaptopurine, thiazide diuretics, theophylline or medications containing aspirin (>325 mg/day) or other salicylates • Concurrent therapy with colchicine, naproxene, indomethacin if not used for gout flares prophylaxis • Body Mass Index (BMI) >50 kilogram per square meter (kg/m²) • A history or presence of xanthinuria, active liver disease or hepatic dysfunction judged clinically relevant in the opinion of the Investigator • Other concurrent severe diseases (cancer, AIDS, thyroid disease etc.) judged clinically relevant in the opinion of the Investigator • Subjects with AST and ALT and total bilirubin more than 1.5 x Upper Normal Limit • Positive history for organ transplantation • Dementia, psychosis, alcoholism (> 350 g ethanol/week) or chronic abuse of medicines, drugs or psychoactive substances • Introduction of concurrent therapies among those not permitted and which cannot be suspended without harm to the subject • Hypersensitivity or contraindications to use of the product under study • Participation in other pharmacological clinical trials in the previous 4 months • Conditions which in the Investigator’s opinion may interfere with the study’s execution or due to which the subject should not participate for safety reasons • Risk of low subject cooperation • Females of childbearing potential not using adequate contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner • Lactose intolerance |
| Creatinina sierica >1.5 mg/dL o clearance della creatinina calcolata < 60 mL/min; Donne in gravidanza o allattamento; evidenza clinica allo screening di cardiopatia ischemica o insufficienza cardiaca congestizia; Terapia concomitante con Losartan; Terapia concomitante con agenti che riducono l'urato, azathioprine, 6-mercaptopurine, diuretici tiazidici, teofilline o farmaci che contengono aspirina(>325 mg/die) o altri salicilati; terapie concomitanti con colchicina, naprossene, indometacina se non utilizzati come profilassi per gli attacchi acuti gottosi; Indice di Massa Corporea (BMI) >50 mg/m²; storia o presenza di xantinuria, disfunzioni epatiche attive o altre disfunzioni epatiche considerate clinicamnete rilevanti nel giudizio dello sperimentatore; altre patologie concomitanti (tumori, AIDS, problemi alla tiroide etc); ALT e AST e bilirubina totale maggiore di 1.5 x UNL; Storia di trapianto di organi; demenza, psicosi, alcolismo (> 350 g etanolo/settimana) o abuso cronico di farmaci, droghe o sostanze psicoattive; introduzione di terapie concomitanti tra quelle non permesse e che non possono essere sospese senza mettere a rischio il soggetto; ipersensibilità o controindicazioni ad utilizzare i prodotti in studio; partecipazione in altri studi clinici farmacologici nei 4 mesi precedenti; condizioni che nel giudizio dello sperimentatore possono interferire con l'esecuzione dello studio, o per le quali il soggetto non dovrebbe partecipare per ragioni di sicurezza; rischio di poca collaborazione da parte del soggetto; donne in età fertile che non utilizzano adeguati sistemi di contraccezione quali impianti, iniettabili, contraccettivi combinati orali, device intrauterini, astinenza sessuale o vasectomia del partner; intolleranza al lattosio |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage of subjects with serum urate levels < 6.0 mg/dL after 4 weeks of treatment |
| percentuale di soggetti con urato sierico < 6.0 mg/dL dopo 4 settimane di trattamento |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Percentage of subjects, in each treatment group, as defined at visit 1, with the serum urate levels <6.0 mg/dL after 8 weeks of treatment (visit 2). Percentage of subjects, in each treatment group, as defined at visit 2, with the last 3 serum urate levels (at 16, 20 and 24 weeks from the treatment start) < 6.0 mg/dL after 24 weeks of treatment (end of study) overall and within each of the three subgroups of subjects defined by baseline urate concentration (less than 9.0 mg/dL, at least 9.0 mg/dL but less than 10 mg/dL, 10 mg/dL or more). Percentage of subjects with serum urate levels <6.0 mg/dL at each study visit (after 12, 16, 20, 24 weeks of treatment). Mean values and percent reduction from baseline in serum urate levels, at each visit. Percentage of subjects with gout flares during the 24 weeks of treatment |
| Percentuale di soggetti, in ciascun gruppo di trattamento, come definito alla visita 1, con i livelli sierici di urato <6,0 mg / dL dopo 8 settimane di trattamento (visita 2). Percentuale di soggetti, in ciascun gruppo di trattamento, come definiti alla visita 2, con gli ultimi 3 livelli sierici di urato (a 16, 20 e 24 settimane dall'inizio del trattamento) <6,0 mg / dL dopo 24 settimane di trattamento (fine dello studio) globali e suddivisi nei tre sottogruppi definiti dalla concentrazione di urato al basale (< 9,0 mg / dL, almeno 9,0 mg / dL, ma < 10 mg / dL, 10 mg / dL o più). Percentuale di soggetti con livelli sierici di urato <6,0 mg / dL ad ogni visita di studio (dopo il 12, 16, 20, 24 settimane di trattamento). I valori medi e la riduzione percentuale rispetto al basale dei livelli sierici di urato, ad ogni visita. Percentuale di soggetti con attacchi acuti di gotta durante le 24 settimane di trattamento. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | Yes |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| - Stesso farmaco ad altro dosaggio |
| - same IMP used at different dosage |
|
| 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 | 32 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 68 |
| 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
|
|
| 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 | 20 |
| 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 | 20 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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