E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hyperuricemia and gout |
hiperuricemia y gota |
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E.1.1.1 | Medical condition in easily understood language |
Gout is caused by elevated levels of uric acid in the blood which crystallize, and the crystals are deposited in joints, tendons, and surrounding tissues. |
La gota es causada por niveles elevados de ácido úrico en la sangre que cristalizan, y los cristales se depositan en las articulaciones, tendones y tejidos circundantes. |
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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 | 15.1 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020907 |
E.1.2 | Term | Hyperuricemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 primary 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 (week 4), whose serum urate concentrations will be below 6 mg/dL (357 µmol/L). |
El objetivo primario del estudio consiste en determinar si el febuxostat 80 mg, administrado una vez al día, es mejor que el alopurinol 300 mg/día, considerando la proporción de sujetos que, en la consulta 1 (es decir, después de cuatro semanas de tratamiento), tienen una concentración de urato sérico inferior a 6 mg/dl (357 µmol/l). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are the evaluation of the efficacy of Febuxostat 80 mg, 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 evaluation of 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 (week 8) whose serum urate concentrations will be below 6 mg/dL (357 µmol/L) and considering the proportion of subjects at visit 6 (week 24), whose last 3 monthly (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 (visit 1, 2, 3, 4, 5 and 6).
Evaluation of the effect of urate lowering therapy to gout flare incidence during the study. |
Evaluación de la eficacia del feb. 80mg, administrado después de 4 sem. de trat. con alop.300mg, en la reducción de urato serico por debajo de 6mg/dl en la consulta2 (ocho semanas después de la aleatorización). Evaluación de la eficacia del feb.120mg adm. una vez al día, después de 4 sem. de trat. con feb.80mg, con respecto al feb. 80 mg y al alop.300mg/día, considerando el porcentaje de sujetos con urato serico inferior a 6mg/dl (357µmol/l) en la consulta 2 (después de 8 semanas de tratamiento) y considerando, en la consulta 6, la proporción de sujetos que en los últimos 3 meses (respectivamente, en las sem.16,20y24) tenían urato serico inferior a 6mg/dl (357µmol/l). Comparación de la eficacia del feb 80y120mg, adm. una vez al día, con respecto al alop.300mg/día, desde la evaluación de la concentración de urato sérico en cada consulta (consultas1 2,3, 4,5y6). Evaluación del efecto de la terapia para la reducción del urato en la incidencia de los ataques agudos gotosos en el estudio. |
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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
Serum uric acid ? 8.0 milligrams per decilitre (mg/dL) at baseline
Subject willing to comply with the prophylaxis treatment |
Sujetos de ambos sexos con hiperuricemia, que han sufrido al menos un episodio agudo de gota en su historia clínica.
Los signos y síntomas del ataque agudo de gota deben ser resueltos al menos 48 horas antes del control o de la aleatorización.
Varones o mujeres de 18 años o más.
Sujetos dispuestos y capaces de dar su consentimiento informado por escrito.
Conformidad con los criterios preliminares de la Asociación Americana de Reumatología para la clasificación de la artritis aguda de gota primaria.
Niveles séricos de ácido úrico ? 8,0 miligramos por decilitro (mg/dl), a la concentración basal.
Sujetos dispuestos a recibir el tratamiento profiláctico. |
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E.4 | Principal exclusion criteria |
Serum creatinine >1.5 mg/dL or calculated creatinine clearance < 60 milliliters per minutes (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 sérica > 1,5 mg/dl o aclaramiento de la creatinina calculada < 60 mililitros por minuto (ml/min).
Embarazo o lactancia.
Evidencia clínica de cardiopatía isquémica o insuficiencia cardiaca congestiva en la consulta de control.
Terapia concomitante con losartán.
Terapia concomitante con agentes que reducen los niveles de urato, azatioprina, 6-mercaptopurina, diuréticos tiazídicos, teofilinas o fármacos que contienen aspirina (> 325 mg/día) u otros salicilatos.
Terapia concomitante con colchicina, naproxeno o indometacina, si no se utilizan para la profilaxis de los ataques agudos de gota.
Índice de masa corporal (BMI) > 50 kg por metro cuadrado (kg/m²).
Historia o presencia de xantinuria, enfermedad hepática activa o disfunción hepática clínicamente relevantes a juicio del experimentador.
Otras patologías concomitantes graves (cáncer, SIDA, enfermedades de la glándula tiroides etc.) consideradas clínicamente relevantes por el experimentador.
Sujetos con AST y ALT y bilirrubina total más de 1,5 veces superior al límite superior normal.
Trasplante previo de órganos.
Demencia, psicosis, alcoholismo (> 350 g de etanol/semana) o abuso crónico de fármacos, estupefacientes o sustancias psicoactivas.
Introducción de terapias concomitantes entre las no permitidas y que no pueden ser suspendidas sin causar daños al sujeto.
Hipersensibilidad o contraindicaciones para el uso de los productos estudiados.
Participación en otros estudios clínicos farmacológicos en los cuatro meses anteriores.
Condiciones que, a juicio del experimentador podrían interferir con la realización del estudio o por las cuales el sujeto no debería participar por motivos de seguridad.
Riesgo de escasa colaboración por parte del sujeto.
Mujeres en edad fértil que no utilizan adecuadas precauciones anticonceptivas (implantes, inyectables, anticonceptivos orales combinados, dispositivos intrauterinos, abstinencia sexual o vasectomía de la pareja).
Intolerancia a la lactosa. |
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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 (visit 1). |
Porcentaje de sujetos con niveles séricos de urato < 6,0 mg/dl después de cuatro semanas de tratamiento (consulta 1). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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. |
Porcentaje de sujetos, en cada grupo de tratamiento definido en la consulta 1, con niveles séricos de urato < 6,0 mg/dl después de ocho semanas de tratamiento (consulta 2).
Porcentaje de sujetos, en cada grupo de tratamiento definido en la consulta 2, con los últimos tres niveles séricos de urato (a 16, 20 y 24 semanas del inicio del tratamiento) < 6,0 mg/dl después de veinticuatro semanas de tratamiento (final del estudio), globales y divididos en los tres subgrupos definidos por la concentración basal de urato (inferior a 9,0 mg/dl, entre 9,0 y menos de 10 mg/dl, 10 mg/dl o más).
Porcentaje de sujetos con niveles séricos de urato < 6,0 mg/dl en cada consulta de estudio (después de 12, 16, 20 y 24 semanas de tratamiento).
Los valores medios y la reducción porcentual con respecto a la concentración basal de los niveles séricos de urato, en cada consulta.
Porcentaje de sujetos con ataques agudos de gota durante las veinticuatro semanas de tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See above E.5.2 |
véase E.5.2 |
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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 | 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 | 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 | No |
E.8.2.3 | Other | No |
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 | 7 |
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
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |