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    Summary
    EudraCT Number:2020-003312-27
    Sponsor's Protocol Code Number:D9480C00018
    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:2023-03-16
    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 number2020-003312-27
    A.3Full title of the trial
    Phase IV, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate (SZC) for the Management of Hyperkalaemia in Patients with Symptomatic Heart Failure with Reduced Ejection Fraction and Receiving Spironolactone (REALIZE-K)
    Ensayo en fase IV, de doble ciego, controlado con placebo, de retirada aleatorizada, para evaluar el uso de ciclosilicato de sodio y zirconio (CSZ) para el tratamiento de la hiperpotasemia en pacientes con insuficiencia cardíaca sintomática con fracción de eyección reducida y que reciben espironolactona (REALIZE-K)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) for the Management of High Potassium in Patients with Symptomatic Heart Failure with Reduced Ejection Fraction and Receiving Spironolactone
    Un estudio para evaluar la eficacia y la seguridad de ciclosilicato de sodio y zirconio (CSZ) para el tratamiento de la hiperpotasemia en pacientes con insuficiencia cardíaca sintomática con fracción de eyección reducida y que reciben espironolactona
    A.3.2Name or abbreviated title of the trial where available
    REALIZE-K
    REALIZE-K
    A.4.1Sponsor's protocol code numberD9480C00018
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04676646
    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 SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointInformation Center
    B.5.3 Address:
    B.5.3.1Street Address1800 Concord Pike
    B.5.3.2Town/ cityWilmington DE
    B.5.3.3Post code19803
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.center@astrazeneca.com
    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 Yes
    D.2.1.1.1Trade name Lokelma
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameSodium zirconium cyclosilicate 5 g.
    D.3.4Pharmaceutical form Powder for oral suspension
    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 INNSODIUM ZIRCONIUM CYCLOSILICATE
    D.3.9.1CAS number 242800-27-7
    D.3.9.2Current sponsor codeSZC
    D.3.9.3Other descriptive nameSZC
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(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 Yes
    D.2.1.1.1Trade name Lokelma
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameSodium zirconium cyclosilicate 10 g.
    D.3.4Pharmaceutical form Powder for oral suspension
    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 INNSODIUM ZIRCONIUM CYCLOSILICATE
    D.3.9.1CAS number 242800-27-7
    D.3.9.2Current sponsor codeSZC
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 placeboPowder for oral suspension
    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
    Hyperkalemia in Patients with Symptomatic Heart Failure
    Hiperpotasemia en pacientes con insuficiencia cardíaca sintomática
    E.1.1.1Medical condition in easily understood language
    Hyperkalemia means that the potassium level in the blood is higher than normal
    La hiperpotasemia significa que el nivel de potasio en la sangre es más alto de lo normal
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10020646
    E.1.2Term Hyperkalaemia
    E.1.2System Organ Class 10027433 - Metabolism and nutrition disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To evaluate the efficacy of SZC as compared with placebo in keeping potassium levels within the normal range (3.5-5.0 mEq/L) while on spironolactone ≥25 mg daily without assistance of rescue therapy for hyperkalaemia (HK)
    - Evaluar la eficacia de SCZ en comparación con el placebo en el mantenimiento de los niveles de potasio dentro del intervalo normal (3,5-5,0 mEq/l) durante la administración de 25 mg o más de espironolactona al día, sin ayuda del tratamiento de rescate para la hiperpotasemia (HK)
    E.2.2Secondary objectives of the trial
    - To compare the SZC and placebo arms with respect to keeping potassium levels within a normal range (3.5-5.0 mEq/L), keeping same spironolactone dose as used at randomisation, and without having had assistance of rescue therapy for HK
    - To compare the SZC and placebo arms with respect to spironolactone dose
    - To evaluate the efficacy of SZC as compared to placebo in keeping potassium levels ≤5.0 mEq/L
    - To compare the SZC and placebo arms with respect to ability to prevent decreases in spironolactone dose
    - To compare the SZC and placebo arms with respect to change from randomisation in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)
    - To assess the safety and tolerability of SZC as compared to placebo in patients with HFrEF and HK, who are on RAASi treatment
    - Comparar los grupos de CSZ y placebo en cuanto al mantenimiento de los niveles de potasio dentro de un intervalo normal (3,5-5,0 mEq/l), mantener la misma dosis de espironolactona que la utilizada en la aleatorización, y sin haber recibido ayuda del tratamiento de rescate para la HP
    - Comparar los grupos de CSZ y placebo con respecto a la dosis de espironolactona
    - Evaluar la eficacia de CSZ en comparación con el placebo para mantener los niveles de potasio ≤5,0 mEq/l
    - Comparar los grupos de CSZ y de placebo con respecto a la capacidad de impedir disminuciones en la dosis de espironolactona
    - Comparar los grupos de CSZ y de placebo con respecto al cambio desde la aleatorización en la puntuación del resumen clínico del cuestionario de miocardiopatía de Kansas City (KCCQ-CSS)
    - Evaluar la seguridad y la tolerabilidad de CSZ en comparación con placebo en pacientes con ICr y HP que están recibiendo tratamiento con RAASi
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Adults aged ≥18 years
    - Potassium and estimated glomerular filtration rate (eGFR):
    - Cohort 1: sK+ 5.1-5.9 mEq/L at screening/study enrolment and eGFR ≥30 mL/min/1.73 m2; or
    - Cohort 2: Normokalaemic (sK+ 3.5-5.0 mEq/L) at screening and ‘at risk’ of developing HK defined as any of the following:
    - Have a history of HK (sK+ >5.0 mEq/L) within the prior 36 months and eGFR ≥30 mL/min/1.73 m2, or
    - sK+ 4.5-5.0 mEq/L and eGFR 30 to 60 mL/min/1.73 m2, or
    - sK+ 4.5-5.0 mEq/L and age >75 years

    - Symptomatic HFrEF (New York Heart Association [NYHA] class II-IV), which has been present for at least 3 months
    - Left ventricular ejection fraction (LVEF) ≤40%

    - Receiving angiotensin-converting enzyme inhibitor (ACEi), angiotensin II receptor blocker (ARB), or angiotensin receptor-Neprilysin inhibitor (ARNi)
    - Not on or on low-dose spironolactone or eplerenone (<25 mg daily).
    - Receiving beta-blocker unless contraindicated.

    Inclusion Criteria for Proceeding to the 6-month Randomised-Withdrawal Treatment Phase:
    - NK (3.5-5.0 mEq/L) on SZC and receiving spironolactone ≥25 mg daily at the end of the 4- to 6-week run-in phase.
    Sex
    -Female:
    - Female participants of childbearing potential must have a negative pregnancy test (serum).
    - Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). They should have been stable on their chosen method of birth control for a minimum of 4 months before entering the study and willing to remain on the birth control until 4 weeks after the last dose.

    Informed Consent
    - Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this CSP
    - Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.
    - Adultos de 18 o más años de edad
    - Tasa de filtración glomerular de potasio y estimada (TFGe):
    - Cohorte 1: sK+ 5,1-5,9 mEq/l en la selección/inclusión en el estudio y TFGe ≥30 ml/min/1,73 m2; o
    - Cohorte 2: Normopotasemia (sK+ 3,5-5,0 mEq/l) en la selección y “en riesgo” de desarrollar HP definida como cualquiera de los casos siguientes:
    - Antecedentes de HP (sK+ >5,0 mEq/l) en los 36 meses anteriores y TFGe ≥30 ml/min/1,73 m2; o
    - sK+ 4,5-5,0 mEq/l y TFGe de 30 a 60 ml/min/1,73 m2; o
    - sK+ 4,5-5,0 mEq/l y edad >75 años

    - ICr sintomática (clase II-IV de la New York Heart Association [NYHA]), presente durante al menos 3 meses
    - Fracción de eyección ventricular izquierda (FEVI) ≤40 %

    - Recibir inhibidores de la enzima convertidora de la angiotensina (IECA), bloqueantes de receptores de la angiotensina II (BRA) o inhibidores de la angiotensina y el receptor de la neprilisina (iARN)
    - No recibir espironolactona o eplerenona en dosis bajas (< 25 mg al día)
    - Recibir betabloqueantes, a menos que esté contraindicado

    Criterios de inclusión para pasar a la fase de tratamiento de retirada aleatorizada de 6 meses:
    - NP (3,5-5,0 mEq/l) con CSZ y recibir 25 mg o más de espironolactona al día al final de la fase de preinclusión.
    Sexo
    - Mujer:
    - Las mujeres en edad fértil deben obtener un resultado negativo en la prueba de embarazo en sangre (suero).
    - Las mujeres participantes deben llevar un año de posmenopausia, ser quirúrgicamente estériles o utilizar un método anticonceptivo altamente eficaz (definido por alcanzar una tasa de fallos inferior al 1 % al año cuando se usa de forma constante y correcta). Deben haber usado el método anticonceptivo elegido de manera estable durante un mínimo de 4 meses antes de entrar en el estudio y mantenerlo hasta 4 semanas después de la última dosis.

    Consentimiento informado
    - Capacidad de otorgar consentimiento informado firmado, como se describe en el Apéndice A, lo que incluye el cumplimiento de los requisitos y las restricciones enumerados en el formulario de consentimiento informado (FCI) y en este protocolo
    - Entrega de un consentimiento informado por escrito, firmado y fechado, de Información de investigación genética opcional antes de la recogida de muestras para la investigación genética opcional en apoyo de la Iniciativa genómica [Genomic Initiative].
    E.4Principal exclusion criteria
    - Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or severe stenotic valve disease as a primary cause of HF
    - Current inpatient hospitalization with unstable HF, defined as any of the following:
    a. SBP <95 mmHg during the 6 hours prior to screening.
    b. Intravenous diuretic therapy during the 12 hours prior to screening.
    c. Use of intravenous inotropic drugs during the 24 hours prior to screening.
    d. Received mechanical circulatory support during the 48 hours prior to screening.

    - Type 1 myocardial infarction (MI), unstable angina, or stroke within 12 weeks prior to enrolment
    - Coronary revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these procedures
    - Implantation of a Cardiac Resynchronisation Therapy (CRT) device within 12 weeks prior to enrolment or intent to perform atrial fibrillation ablation or to implant a CRT device
    - Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
    - Clinically significant bradycardia, as per investigator’s judgement, or second- or thirddegree heart block without a pacemaker
    - Previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or transplantation or implantation expected after randomisation
    - History of gynecomastia due to spironolactone therapy requiring down-titration or discontinuation of spironolactone, or switch to a different MRA


    Other Exclusions
    - Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
    - Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
    - Previous enrolment in the present study.
    - For women only - breast-feeding or planning to become pregnant during the study.
    - If the participant has evidence of Coronavirus disease 2019 (COVID-19) within 2 weeks prior to enrolment (see Appendix E), the participant cannot be enrolled in the study.
    - Insuficiencia cardíaca (IC) por miocardiopatía restrictiva, miocarditis activa, pericarditis constrictiva, miocardiopatía hipertrófica (obstructiva) o valvulopatía estenótica grave como causa principal de la IC
    - Hospitalización actual con IC inestable, definida como cualquiera de los casos siguientes:
    a. TAS <95 mmHg durante las 6 horas previas a la selección.
    b. Terapia diurética intravenosa durante las 12 horas previas a la selección.
    c. Uso de fármacos inotrópicos intravenosos durante las 24 horas previas a la selección.
    d. Haber recibido apoyo circulatorio mecánico durante las 48 horas anteriores a la selección.
    - Infarto de miocardio (IM) de tipo 1, angina inestable o ictus en las 12 semanas anteriores a la inscripción
    - Revascularización coronaria (intervención coronaria percutánea [ICP] o injerto de derivación coronaria [CABG]) o reparación/reemplazo valvular en las 12 semanas anteriores a la inscripción, o previsión de someterse a cualquiera de estos procedimientos
    - Implantación de un dispositivo de terapia de resincronización cardíaca (TRC) en las 12 semanas anteriores a la inscripción, o intención de realizar una ablación de la fibrilación auricular o de implantar un dispositivo de TRC
    - Fibrilación auricular sintomática o no controlada a pesar del tratamiento, o taquicardia ventricular sostenida asintomática. Están permitidos los pacientes con fibrilación auricular controlada con medicación
    - Bradicardia clínicamente significativa según el criterio del investigador, o bloqueo cardíaco de segundo o tercer grado sin marcapasos
    - Trasplante cardíaco previo o implante de un dispositivo de asistencia ventricular (DAV) o un dispositivo similar, o trasplante o implante previstos después de la aleatorización
    - Antecedentes de ginecomastia por tratamiento con espironolactona que requiere ajuste a la baja o interrupción de la espironolactona, o cambio a una ARM diferente

    Otras exclusiones
    - Participación en la planificación o realización del estudio (aplicable al personal de AstraZeneca o al personal del centro del estudio)
    - Determinación por parte del investigador de que el participante no debe participar en el estudio si es poco probable que cumpla con los procedimientos, las restricciones y los requisitos del estudio
    - Inscripción previa en el estudio actual
    - Solo para mujeres: en periodo de lactancia o con expectativa de embarazo durante el estudio
    - Si el participante presenta signos de enfermedad por coronavirus 2019 (COVID-19) en las 2 semanas anteriores a la inscripción (ver el Apéndice E), no se puede inscribir al participante en el estudio
    E.5 End points
    E.5.1Primary end point(s)
    Occurrence (yes/no) of patients on SZC compared to placebo who, at the end of treatment visit, have serum potassium within 3.5-5.0 mEq/L, are on spironolactone ≥25 mg daily, and did not use rescue therapy for HK at any point during the randomised-withdrawal phase.
    Aparición (sí/no) de pacientes tratados con SCZ en comparación con el placebo que, en la visita de final del tratamiento, tienen potasio sérico (sK+) en un intervalo de 3,5 a 5,0 mEq/l, reciben espironolactona ≥25 mg al día y no han recibido tratamiento de rescate para la HP en ningún momento durante la fase de retirada aleatorizada.
    E.5.1.1Timepoint(s) of evaluation of this end point
    From randomisation to the end of treatment (EOT) visit (approximately 6 months post-randomisation)
    Desde la aleatorización hasta la visita final del tratamiento (FdT) (aproximadamente 6 meses después de la aleatorización)
    E.5.2Secondary end point(s)
    - Occurrence (yes/no) of patients on SZC compared to placebo who, at the EOT visit, have sK+ within 3.5-5.0 mEq/L are on the same dose of spironolactone as they were on at randomisation, and did not use rescue therapy for HK at any point during the randomised-withdrawal phase.

    - Occurrence (yes/no) of patients on SZC compared to placebo who, at the EOT visit are on spironolactone ≥25 mg daily.

    - Time to first HK episode for patients on SZC compared to placebo during the randomised withdrawal phase, with HK defined as sK+ >5.0 mEq/L

    - Time to first instance of decrease or discontinuation of spironolactone dose due to HK for patients on SZC compared to placebo during the randomised-withdrawal phase

    - Change in KCCQ-TSS at EOT visit from randomisation for patients on SZC compared to placebo
    - Aparición (sí/no) de pacientes tratados con CSZ en comparación con el placebo que, en la visita de final del tratamiento (FdT), tienen sK+ en un intervalo de 3,5 a 5,0 mEq/l reciben la misma dosis de espironolactona que la que recibieron en la aleatorización y no han recibido tratamiento de rescate para la HP en ningún momento durante la fase de retirada aleatorizada.

    - Aparición (sí/no) de pacientes tratados con CSZ en comparación con el placebo que, en la visita de FdT, reciben 25 mg o más de espironolactona al día.

    - Tiempo hasta el primer episodio de HP en pacientes con CSZ en comparación con placebo durante la fase de retirada aleatorizada, con HP definida como sK+ >5,0 mEq/l.

    - Tiempo hasta el primer caso de disminución o interrupción de la dosis de espironolactona debido a HP en pacientes con CSZ en comparación con placebo durante la fase de retirada aleatorizada.

    - Cambio en el KCCQ-CSS en la visita de FdT desde la aleatorización para los pacientes tratados con CSZ en comparación con el placebo.
    E.5.2.1Timepoint(s) of evaluation of this end point
    From randomisation to the end of treatment (EOT) visit (approximately 6 months post-randomisation)
    Desde la aleatorización hasta la visita final del tratamiento (FdT) (aproximadamente 6 meses después de la aleatorización)
    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 No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA17
    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
    Brazil
    Canada
    United States
    Ukraine
    Czechia
    Hungary
    Poland
    United Kingdom
    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
    UVUP
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months8
    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: 214
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 214
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 345
    F.4.2.2In the whole clinical trial 400
    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)
    For patients who will not continue on commercially available SZC after study completion, the investigator should return the patients to their original spironolactone dose prior to study enrolment and manage the patient as per standard of care.
    En el caso de los pacientes que no continúen con el CSZ disponible comercialmente después de la finalización del estudio, el investigador debe devolver a los pacientes a su dosis original de espironolactona antes de la inscripción en el estudio y tratar al paciente según el tratamiento estándar.
    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 Decision2023-03-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-02-25
    P. End of Trial
    P.End of Trial StatusOngoing
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