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    Summary
    EudraCT Number:2016-004395-22
    Sponsor's Protocol Code Number:402-C-1603
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-11-07
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2016-004395-22
    A.3Full title of the trial
    A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome
    Un ensayo de fase 2/3 sobre la eficacia y seguridad de la bardoxolona metilo en pacientes con síndrome de Alport
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    clinical study to evaluate the efficacy and safety of a new drug (Bardoxolone methyl) in the treatment of subjects with Alport syndrome
    Estudio clínico para evaluar la eficacia y la seguridad de un nuevo fármaco (Bardoxolone methyl) en el tratamiento de sujetos con síndrome de Alport
    A.3.2Name or abbreviated title of the trial where available
    CARDINAL
    A.4.1Sponsor's protocol code number402-C-1603
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03019185
    A.5.4Other Identifiers
    Name:IND numberNumber:131763
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorReata Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportReata Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationReata Pharmaceuticals, Inc
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street Address2801 Gateway Drive, Suite 150
    B.5.3.2Town/ cityIrving
    B.5.3.3Post codeTX 75063
    B.5.3.4CountryUnited States
    B.5.4Telephone number0014694424838
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBardoxolone Methyl
    D.3.2Product code RTA 402
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNbardoxolone methyl
    D.3.9.1CAS number 218600-53-4
    D.3.9.2Current sponsor codeRTA 402
    D.3.9.3Other descriptive nameBARDOXOLONE METHYL
    D.3.9.4EV Substance CodeSUB33044
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBardoxolone Methyl
    D.3.2Product code RTA 402
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNbardoxolone methyl
    D.3.9.1CAS number 218600-53-4
    D.3.9.2Current sponsor codeRTA 402
    D.3.9.3Other descriptive nameBARDOXOLONE METHYL
    D.3.9.4EV Substance CodeSUB33044
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Alport Syndrome
    Síndrome de Alport
    E.1.1.1Medical condition in easily understood language
    Alport syndrome is a rare genetic disorder characterized by progressive kidney disease and abnormalities of the ears and eyes.
    El síndrome de Alport es un trastorno genético raro caracterizado por enfermedad renal progresiva y anomalías de las orejas y los ojos.
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10001843
    E.1.2Term Alport's syndrome
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase 2:
    - To assess the change from baseline in estimated glomerular filtration rate (eGFR) in bardoxolone methyl-treated patients after 12 weeks of treatment.
    - To assess the safety of bardoxolone methyl after 12 weeks of treatment.
    Phase 3:
    - To assess the change from baseline in estimated glomerular filtration rate (eGFR) in bardoxolone methyl-treated patients relative to placebo after 48 weeks of treatment.
    - To assess the safety of bardoxolone methyl relative to placebo after 48 weeks of treatment.
    Fase 2:
    - Valorar el cambio desde el punto de partida en tasa de filtración glomerular estimada (estimated glomerular filtration rate o eGFR) en pacientes tratados con bardoxolona metilo tras 12 semanas de tratamiento.
    - Valorar la seguridad de la bardoxolona metilo tras 12 semanas de
    tratamiento.
    Fase 3:
    - Valorar el cambio desde el punto de partida en tasa de filtración glomerular estimada (estimated glomerular filtration rate o eGFR) en pacientes de bardoxolona metilo tratados con placebo tras 48 semanas de tratamiento.
    - Valorar la seguridad de la bardoxolona metilo en tratamiento de placebo tras 48 semanas de tratamiento.
    E.2.2Secondary objectives of the trial
    Phase 2:
    - To assess the safety and efficacy of bardoxolone methyl after 48 and 100 weeks of treatment.
    Exploratory
    - to assess the safety and efficacy of bardoxolone methyl at Week 52 following a 4-week drug treatment withdrawal period
    Phase 3:
    Key Secondary
    - To assess the change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 52 following a 4-week drug treatment withdrawal period.
    Secondary
    - To assess the change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo after 100 weeks of treatment.
    - To assess the safety of bardoxolone methyl relative to placebo after 100 weeks of treatment.
    - To assess the change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 104 following a 4-week drug treatment withdrawal period.
    Fase 2:
    - Valorar la seguridad y eficacia de la bardoxolona metilo tras 48 y 100 sem. de tratamiento.
    Exploratorios:
    - Evaluar la seguridad y eficacia de la bardoxolona metilo en la sem. 52, tras un periodo de retirada de 4 sem. del tratamiento con el fármaco.
    Fase 3: clave:
    - Valorar el cambio desde el punto de partida en tasa de filtración glomerular estimada (eGFR) en pacientes de bardoxolona metilo tratados con placebo en la sem. 52 tras un periodo de retirada del tratamiento con el fármaco de 4 sem.
    - Valorar el cambio desde el punto de partida en eGFR en pacientes de bardoxolona metilo tratados con placebo tras 100 sem. de tratamiento.
    - Valorar la seguridad de la bardoxolona metilo en tratamiento de placebo tras 100 sem. de tratamiento.
    - Valorar el cambio desde el punto de partida en tasa de filtración glomerular estimada (eGFR) en pacientes de bardoxolona metilo tratados con placebo en la sem. 104 tras un periodo de retirada del tratamiento con el fármaco de 4 sem.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male and female patients 18 ≤ age ≤ 60 upon study consent;
    2. Diagnosis of Alport syndrome by genetic testing (documented mutation in a gene associated with Alport syndrome, including COL4A3, COL4A4, or COL4A5) or histologic assessment using electron microscopy;
    3. Screening eGFR (average of Screen A and Screen B eGFR values) ≥ 30 and ≤ 90 mL/min/1.73 m2. The two eGFR values collected at Screen A and Screen B visits used to determine eligibility must have a percent difference ≤ 25%;
    4. Albumin to creatinine ratio (ACR) ≤ 3500 mg/g at Screen B visit;
    5. Receiving an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB), at the maximally tolerated labeled daily dose (MTLDD), as defined in Section 9.1.7, for at least 6 weeks prior to the Screen A visit. The dosage of ACE inhibitor and/or ARB should remain the same throughout the remainder of the study (i.e., no change in dosage or medication), and any potential changes should be discussed with the medical monitor. Patients not taking an ACE inhibitor and/or ARB because of a medical contraindication may be eligible if they have discontinued treatment at least 8 weeks prior to the Screen A visit (these patients must be discussed with medical monitor prior to enrollment);
    6. Adequate bone marrow reserve and organ function at the Screen A visit as follows:
    a. Hematologic: Absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L,
    hemoglobin (Hgb) ≥ 9 g/dL;
    b. Hepatic: Total bilirubin (TBL) ≤ 1.5X the upper limit of normal (ULN), alanine
    aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5X ULN;
    7. Able to swallow capsules;
    8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
    9. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study prior to initiation of any patient-mandated procedures.
    1. Pacientes hombres y mujeres 18 ≤ de edad ≤ 60 tras consentimiento del estudio;
    2. Diagnosis del síndrome de Alport por prueba genética (mutación documentada en un gene asociado al síndrome de Alport, incluyendo COL4A3, COL4A4, o COL4A5) o valoración histológica utilizando nicroscopio electrónico;
    3. Exploración eGFR (promedio de valores eGFR en Exploración A y Exploración B) ≥ 30 y ≤ 90 mL/min/1.73 m2. Los dos valores eGFR recogidos en las visitas de exploración A y exploración B utilizadas para determinar la adecuación deben tener una diferencia en porcentaje ≤ 25%;
    4. Ratio de albúmina a creatinina (Albumin to Creatinine Ratio o ACR) ≤ 3500 mg/en la vista de Exploración B;
    5. Reciben un inhibidor de enzima convertidora de angiotensina (Angiotensin-Converting Enzyme o ACE) y/o un bloqueador de receptor II de angiotensina (Angiotensin II Receptor Blocker o ARB), a la máxima dosis diaria tolerada etiquetada (MTLDD), según se define en la sección 9.1.7 durante 6 semanas como mínimo antes de la visita Exploración A. La dosificación del inhibidor ACE y/o ARB debe mantenerse igual durante todo el estudio (no cambiar la dosis ni la medicación) y cualquier cambio potencial deberá consultarse con el monitor médico. Los pacientes que no tomen un inhibidor ACE y/o ARB por contraindicación médica pueden ser idóneos si han dejado el tratamiento 8 semanas antes como mínimo de la visita Exploración A (La participación de estos pacientes deberá comentarse con el monitor médico antes de su inclusión);
    6. Adecuada reserva de medula ósea y función orgánica en la vista Exploración A, tal como se indica a continuación:
    a. Hematológica: Recuento absoluto de neutrófilos > 1.5 x 109/L, plaquetas > 100 x 109/L, hemoglobina (Hgb) ≥ 9 g/dL;
    b. Hepática: Bilirrubina total (TBL) ≤ 1,5X el límite superior normal (Upper Limit of Normal o ULN), alanina aminotransferasa (Alanine aminotransferase o ALT) y aspartato aminotransferasa (aspartate aminotransferase o AST) ≤ 1,5X ULN;
    7. Capaz de tragar cápsulas;
    8. Dispuesto y capaz de cumplir las visitas programadas, plan de tratamiento, pruebas de laboratorio y otros procedimientos del estudio;
    9. Prueba de un documento de consentimiento informado datado y firmado personalmente indicando que el paciente ha sido informado de todos los aspectos pertinentes del estudio antes del inicio de cualquier procedimiento exigido en el protocolo
    E.4Principal exclusion criteria
    1. Prior exposure to bardoxolone methyl;
    2. Ongoing chronic hemodialysis or peritoneal dialysis therapy;
    3. Renal transplant recipient;
    4. B-type natriuretic peptide (BNP) level >200 pg/mL at Screen A visit;
    5. Uncontrolled diabetes (HbA1c >11.0%) at Screen A visit;
    6. Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
    7. Serum albumin < 3 g/dL at Screen A visit;
    8. History of clinically significant left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
    a. Clinically significant congenital or acquired valvular disease;
    b. Left ventricular ejection fraction < 40% (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
    c. Pericardial constriction (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
    d. Restrictive or congestive cardiomyopathy (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
    e. Symptomatic coronary disease (prior myocardial infarction, percutaneous
    coronary intervention, coronary artery bypass graft surgery, or angina);
    f. History of hospitalization for heart failure;
    g. Cardiac insufficiency, defined as New York Heart Association Class >2;
    h. History of atrial fibrillation;
    i. History of unstable arrhythmias;
    9. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic BP > 100 mm Hg at Screen A visit after a period of rest;
    10. Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
    11. History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
    12. Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study.
    13. Untreated or uncontrolled active bacterial, fungal, or viral infection;
    14. Participation in other investigational clinical studies within 30 days prior to Day 1;
    15. Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) during Screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested;
    16. Women who are pregnant or breastfeeding;
    17. Known hypersensitivity to any component of the study drug;
    18. Any abnormal laboratory level that, in the opinion of the investigator, would put the patient at risk by trial enrollment;
    19. Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.
    1. Exposición previa al bardoxolona metilo;
    2. Hemodiálisis crónica actual o terapia para diálisis peritoneal;
    3. Receptor de trasplante renal;
    4. Nivel péptido natriurético tipo B (B-type Natriuretic Peptide o BNP) > 200 pg/mL en visita Exploración A;
    5. Diabetes no controlada (HbA1c > 11,0%) en visita Exploración A;
    6. Diálisis aguda o lesión aguda de riñón en un plazo de 12 semanas antes de la visita Exploración A o durante la Exploración;
    7. Seroalbúmina < 3 g/dL en visita Exploración A;
    8. Historia de lesión izquierda del corazón significativa clínicamente y/o enfermedad cardiaca significativa clínicamente, incluyendo pero no estando limitado a lo siguiente:
    a. Enfermedad valvular adquirida o congénita significativa clínicamente.
    b. Fracción de eyección ventricular izquierda < 40% (basada en ecocardiograma realizado en visita Exploración A o en un plazo de 6 meses antes del Día 1);
    c. Constricción pericardial (basada en ecocardiograma realizado en visita Exploración A o en un plazo de 6 meses antes del Día 1);
    d. Cardiomiopatía congestiva o restrictiva (basada en ecocardiograma realizado en visita Exploración A o en un plazo de 6 meses antes del Día 1);
    e. Enfermedad coronaria sintomática (antes de infarto de miocardio agudo, intervención coronaria percutánea, cirugía de baipás coronario, o angina);
    f. Historial de hospitalización por fallo cardiaco;
    g. Insuficiencia cardiaca, definida por la Asociación Cardiaca de Nueva York como de Clase > 2;
    h. Historial de fibrilación auricular;
    i. Historial de arritmias inestables;
    9. Hipertensión sistémica no controlada comprobada en tensión sanguínea (blood pressure o BP) sistólica sentado > 160 mm Hg o BP diastólica sentado > 100 mm Hg en visita Exploración A tras un periodo de descanso;
    10. BP sistólica < 90 mm Hg en visita Exploración A tras un periodo de descanso;
    11. Historial de malignidad en un plazo de 5 años antes de la visita Exploración A, excepto en caso de carcinomas cervicales o epiteliales localizados;
    12. Inmunosupresión sistémica durante más de 2 semanas, acumulativamente, en un plazo de 12 semanas antes de la aleatorización o necesidad anticipada de inmunosupresión durante el estudio;
    13. Infección vírica, bacteriana o micótica no controlada o no tratada;
    14. Participación en otros estudios clínicos en un plazo de 30 días antes del Día 1;
    15. No dispuesto a aplicar métodos adecuados de control de natalidad (tanto hombres con parejas en edad fértil y mujeres en edad de gestación) durante la Exploración, mientras toman el fármaco en estudio, y al menos durante 30 días después de tomar la última dosis del fármaco en estudio;
    16. Mujeres embarazadas o en periodo de lactancia;
    17. Hipersensibilidad conocida a cualquier componente del fármaco en estudio;
    18. Cualquier nivel anormal de laboratorio que, en opinión del investigador, podría constituir un riesgo para el paciente su inscripción en la prueba;
    19. El paciente es, en opinión del investigador, incapaz de cumplir los requisitos del protocolo del estudio o es inadecuado para el estudio por cualquier motivo.
    E.5 End points
    E.5.1Primary end point(s)
    Phase 2
    Change from baseline in eGFR at Week 12.

    Phase 3
    Change from baseline in eGFR relative to placebo at Week 48.
    Fase 2
    Cambio en el punto de partida en tasa de filtraciòn glomerular estimada en la Semana 12.

    Fase 3
    Cambio en el punto de partida en tasa de filtraciòn glomerular estimada en tratamiento de placebo en la Semana 48
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12 and Week 48
    Semana 12 y Semana 48
    E.5.2Secondary end point(s)
    Phase 3
    Key Secondary Efficacy Endpoint
    The change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 52 following a 4-week drug treatment withdrawal period.
    Secondary Efficacy Endpoints
    - The change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 100.
    - The change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 104 following a 4-week drug treatment withdrawal period.
    Exploratory Efficacy Endpoints
    -The percentage of bardoxolone methyl versus placebo patients with an increase/decrease from baseline in eGRF of 30% or more after 48 weeks of treatment.
    -The percentage of bardoxolone methyl versus placebo patients with an increase/decrease from baseline in eGRF of 30% or more after 100 weeks of treatment.
    -The distribution of changes from baseline in eGFR in bardoxolone methyl versus placebo after 48 weeks and 100 weeks of treatment.
    -The Patient Global Impression of CHange (PGIC) scores in bardoxolone methyl-treated patients relative to placebo after 48 weeks and 100 weeks of treatment
    - The Clinical Global Impression-Improvement (CGI-I) scores in bardoxolone methyl-treated patients relative to placebo after 48 weeks and 100 weeks of treatment.
    Safety Endpoints
    Frequency, intensity, and relationship to study drug of AEs and SAEs, and change from baseline in the following assessments: vital sign measurements, 12-lead ECGs, clinical laboratory measurements, and weight.
    Fase 3
    Variable de eficacia secundaria clave:
    El cambio desde el punto de partida en eGFR en pacientes de bardoxolona metilo tratados con placebo en la semana 52 tras un periodo de retirada del tratamiento con el fármaco de 4 semanas.
    Variable de eficacia secundaria:
    - el cambio desde el punto de partida de eGFR en pacientes de bardoxolona metilo tratados con placebo en la semana 100.
    - el cambio desde el punto de partida de eGFR en pacientes de bardoxolona metilo tratados con placebo en la semana 104 tras un periodo de retirada del tratamiento con el fármaco de 4 semanas.
    Variable de eficacia exploratoria:
    - Comparar el porcentaje de pacientes con bardoxolona metilo y con placebo que experimenten un aumento en eGFR desde el punto de partida de un 30% o superior tras 48 semanas de tratamiento.
    - Comparar el porcentaje de pacientes con bardoxolona metilo y con placebo que experimenten una disminución/aumento en eGFR desde el punto de partida de un 30% o superior tras 48 semanas de tratamiento.
    - Comparar el porcentaje de pacientes con bardoxolona metilo y con placebo que experimenten una disminución/aumento en eGFR desde el punto de partida de un 30% o superior tras 100 semanas de tratamiento.
    - Valorar la distribución de los cambios desde el punto de partida en eGFR en pacientes con bardoxolona metilo respecto a placebo tras 48 semanas y 100 semanas de tratamiento.
    - Valorar las puntuaciones de Impresión Global de Cambio en Pacientes (PGIC o Patient Global Impression of Change) en pacientes tratados con bardoxolona metilo respecto a placebo tras 48 y 100 semanas de tratamiento
    - Valorar las puntuaciones de Impresión Clínica Global – Mejora (CGI-I o Clinical Global Impression-Improvement) ) en pacientes tratados con bardoxolona metilo respecto a placebo tras 48 y 100 semanas de tratamiento.
    Variable de seguridad:
    Frecuencia, intensidad y relación con el farmaco del estudio con AE y SAE, y cambio desde el punto de partida en los siguentes valutaciones: medidas de las constantes vitales, 12 derivaciones ECG, pruebas analiticas y peso.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Key Secondary Efficacy Endpoint
    Week 52

    Secondary Efficacy Endpoints
    Week 100 - Week 104

    Explorative Efficacy Endpoints
    Week 48 and Week 100

    Safety Endpoints
    Duration of the study
    Variable de eficacia secundaria clave
    Semana 52

    Variable de eficacia secundaria
    Semana 100 - Semana 104

    Variable de eficacia exploratoria
    Semana 48 - Semana 100

    Variable de seguridad
    duración del estudio
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    France
    Germany
    Spain
    United Kingdom
    United States
    E.8.7Trial 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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 30
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 180
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    none
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-01-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-22
    P. End of Trial
    P.End of Trial StatusOngoing
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