| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Tophaceous Gout |
| Gota Tofácea |
|
| E.1.1.1 | Medical condition in easily understood language |
| Tophaceous Gout |
| Gota Tofácea |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| 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.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the efficacy of lesinurad by Month 6 when used in combination with febuxostat compared to febuxostat monotherapy |
| Determinar la eficacia de lesinurad cuando se utiliza en combinación con febuxostat comparado con febuxostat en monoterapia, en el Mes 6 |
|
| E.2.2 | Secondary objectives of the trial |
- To determine the efficacy of lesinurad by Month 12 when used in combination with febuxostat compared to febuxostat monotherapy
- To determine the safety of lesinurad over 6 months and 12 months when used in combination with febuxostat
- To investigate by a population analysis approach the influence of intrinsic factors (age, sex, race, body weight, renal function, concomitant medication use) on oral clearance of lesinurad
- To determine the effect of lesinurad when used in combination with febuxostat on Health Related Quality of Life and physical function |
- Determinar la eficacia de lesinurad cuando se utiliza en combinación con febuxostat comparado con febuxostat en monoterapia, en el Mes 12
- Determinar la seguridad de lesinurad a lo largo de 6 y 12 meses cuando se utiliza en combinación con febuxostat
- Investigar, mediante análisis poblacional, la influencia de factores intrínsecos (edad, sexo, raza, peso corporal, función renal, uso de medicación concomitante) sobre el aclaramiento de lesinurad oral
- Determinar el efecto de lesinurad sobre la calidad de vida relacionada con la salud y la función física cuando se utiliza en combinación con febuxostat |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subject is able to understand the study procedures, the risks involved and willing to provide written informed consent before the first study related activity.
Subject meets the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.
Subject meets one of the following criteria:
a.subjects who are not currently taking an approved ULT must have an sUA value of > or = 10 mg/dL.
b.subjects entering the study on febuxostat 40 mg or allopurinol > or = 300 mg and < 600 mg daily (> or = 200 mg daily is allowed for subjects with moderate renal impairment - estimated creatinine clearance > or = 30 and < 60 mL/min) must have an sUA value of > or = 8.0 mg/dL.
c.subjects entering the study on febuxostat > or = 80 mg or allopurinol ? 600 mg daily must have an sUA value of > or = 6.0 mg/dL.
Subject must be able to take gout flare prophylaxis with colchicine or NSAID (including Cox-2 selective NSAID) ± PPI.
Subject with at least 1 measurable tophus on the hands/wrists and/or feet/ankles > or = 5 mm and < or = 20 mm in the longest diameter. |
El paciente tiene capacidad de entender los procedimientos del estudio, los riesgos implicados y desea otorgar un consentimiento informado por escrito antes de que se lleve a cabo la primera actividad relacionada con el estudio.
El diagnóstico de gota del paciente cumple con los Criterios de la Asociación Americana de Reumatismo para la Clasificación de Artritis Aguda de Gota Primaria.
El paciente cumple uno de los criterios siguientes:
a.los pacientes que actualmente no estén tomando un ULT aprobado deben presentar un valor AUs ? 10 mg/dl.
b.los pacientes que se incorporen al estudio tomando 40 mg de febuxostat o > o = 300 mg y < 600 mg diarios de alopurinol (se permite que los pacientes con insuficiencia renal moderada - aclaramiento de creatinina estimado > o = 30 y <60 ml/min tomen ? 200 mg diarios) deben presentar un valor de AUs > o = 8,0 mg/dl.
c.los pacientes que se incorporen al estudio tomando > o = 80 mg de febuxostat o > o = 600 mg diarios de alopurinol deben presentar un valor de AUs ? 6,0 mg/dl.
El paciente debe poder tomar un tratamiento profiláctico de los ataques de gota con colchicina o AINE (incluido AINE inhibidor selectivo de la Cox-2) ± IBP.
Paciente con 1 tofo medible, como mínimo, en manos/muñecas y/o pies/tobillos, > o = 5 mm y < o = 20 mm en su diámetro máximo. |
|
| E.4 | Principal exclusion criteria |
Subject with known hypersensitivity or allergy to febuxostat.
Subject who is taking any approved urate-lowering medication other than allopurinol or febuxostat that is indicated for the treatment of gout within 8 weeks of the Screening Visit.
Subject who previously received pegloticase.
Subject who consumes more than 14 drinks of alcohol per week (eg, 1 drink = 5 oz [150 mL] of wine, 12 oz [360 mL] of beer, or 1.5 oz [45 mL] of hard liquor).
Subject with a history or suspicion of drug abuse within the past 5 years.
Subject with a history of myositis/myopathy or rhabdomyolysis.
Subject that requires or may require systemic immunosuppressive or immunomodulatory treatment.
Subject with known or suspected human immunodeficiency virus (HIV) infection.
Subject with a positive test for active hepatitis B or hepatitis C infection.
Subject with a history of malignancy within the previous 5 years with the exception of non-melanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia or treated in situ Grade 1 cervical cancer.
Subject within the last 12 months with: unstable angina, New York Heart Association (NYHA) class III or IV heart failure, myocardial infarction, stroke, or deep venous thrombosis; or subjects currently receiving anticoagulants.
Subject with uncontrolled hypertension.
Subject with an estimated creatinine clearance < 30 mL/min.
Subjects with a creatine kinase > 2.5 x ULN at any time during the Screening Period.
Subject with active peptic ulcer disease requiring treatment.
Subject with a history of xanthinuria, active liver disease, or hepatic dysfunction.
Subject receiving chronic treatment with more than 325 mg of salicylates per day.
Subject taking valpromide, progabide, or valproic acid.
Subject who has received an investigational therapy within 8 weeks or 5 half-lives (whichever is longer) prior to the Screening Visit.
Subject with any other medical or psychological condition, which in the opinion of the Investigator and/or Medical Monitor, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements, or to complete the study. |
Paciente con hipersensibilidad o alergia conocida a febuxostat.
Paciente que toma cualquier medicación para disminuir el urato que no sea alopurinol o febuxostat, indicada para el tratamiento de la gota (por ej., agente uricosúrico) en las 8 semanas anteriores a la Visita de Selección.
Paciente que previamente haya recibido pegloticasa.
Paciente que previamente haya participado en un ensayo clínico con lesinurad (RDEA594) o RDEA806.
Paciente embarazada o dando de lactar.
Paciente que consume más de 14 bebidas alcohólicas por semana (por ej., 1 bebida = 5 oz [150 ml] de vino, 12 oz [360 ml] de cerveza o 1,5 oz [45 ml] de licor fuerte).
Paciente con antecedentes o sospecha de toxicomanía en los últimos 5 años.
Paciente con antecedentes de miositis/miopatía o rabdomiólisis.
Paciente que requiere o pueda requerir tratamiento inmunosupresor o inmunomodulador sistémico (por ej., azatioprina, 6-mercaptopurina, ciclosporina).
Paciente con infección conocida o sospecha de infección por el virus de la inmunodeficiencia humana (VIH).
Paciente con prueba positiva de infección activa por hepatitis B o C.
Paciente con antecedentes de patología maligna en los 5 años previos, excepto cáncer de piel no-melanoma que ha sido tratado sin evidencia de recurrencia, displasia cervical tratada o cáncer de cérvix in situ Grado 1 tratado.
Paciente que en los últimos 12 meses ha presentado: angina inestable, insuficiencia cardiaca de clase III o IV de la Asociación de Cardiología de Nueva York (NYHA), infarto de miocardio, ictus o trombosis venosa profunda (TVP); o pacientes que actualmente reciben anticoagulantes.
Paciente con hipertensión no controlada (presión sistólica superior a 160 mm Hg o presión diastólica superior a 95 mm Hg en mediciones repetidas en dos visitas separadas durante el Periodo de Selección).
Paciente con aclaramiento de creatinina estimado < 30 ml/min calculado con la fórmula de Cockcroft-Gault utilizando el peso corporal ideal.
Paciente con una hemoglobina < 10 g/dl (hombres) o < 9 g/dl (mujeres) en cualquier momento durante el Periodo de Selección.
Paciente con una alanina aminotransferasa (ALT) o aspartato aminotransferasa (AST) > 2,0 x límite superior de normalidad (LSN) en cualquier momento durante el Periodo de Selección.
Paciente con una gamma glutamil transferasa (GGT) > 3 x LSN en cualquier momento durante el Periodo de Selección.
Pacientes con una creatincinasa > 2,5 x LSN en cualquier momento durante el Periodo de Selección.
Paciente con úlcera péptica activa que requiere tratamiento.
Paciente con antecedentes de xantinuria, enfermedad hepática activa o disfunción hepática.
Paciente que recibe un tratamiento crónico con más de 325 mg de salicilatos al día.
Paciente que toma valpromida, progabide, ácido valproico u otros inhibidores conocidos de la epóxido hidrolasa.
Paciente que ha recibido una terapia experimental en las 8 semanas o 5 semividas (lo que dure más) previas a la Visita de Selección.
Paciente con cualquier otra afección médica o psicológica que, a juicio del investigador y/o del monitor médico, podría provocar un riesgo innecesario para el paciente o interferir con la capacidad del paciente para cumplir con los requisitos del protocolo, o completar el estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of subjects with an sUA level that is < 5.0 mg/dL by Month 6 |
| Proporción de pacientes con un nivel de AUs < 5,0 mg/dl en el Mes 6 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Proportion of subjects who experience complete resolution of at least 1 target tophus by Month 12
2. Proportion of subjects with a best tophus response on at least 1 target tophus of complete or partial resolution by Month 12
3. Proportion of subjects with an improvement from Baseline in HAQ-DI of at least 0.25 at Month 12 |
1.Proporción de pacientes que experimenten una resolución completa de, como mínimo, 1 tofo diana en el Mes 12
2.Proporción de pacientes con mejor respuesta de los tofos, sea de resolución completa o parcial, como mínimo en 1 tofo, en el Mes 12
3.Proporción de pacientes con mejoría en el HAQ-DI respecto al valor basal de 0,25 como mínimo en el Mes 12 |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Patient reported outcomes |
| Resultados proporcionados por los pacientes |
|
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 | No |
| 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 |
| Australia |
| Canada |
| New Zealand |
| Poland |
| South Africa |
| Spain |
| Switzerland |
| Ukraine |
| United States |
|
| 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
|
| Last visit last subject |
| Ultima visita del último paciente |
|
| 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 | 6 |
| 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 |
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