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    Summary
    EudraCT Number:2018-004059-18
    Sponsor's Protocol Code Number:17909
    National Competent Authority:Portugal - INFARMED
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-02-14
    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 ConcernedPortugal - INFARMED
    A.2EudraCT number2018-004059-18
    A.3Full title of the trial
    A Multicenter, Randomized, Parallel Group, Double Blind, Active and Placebo Controlled Study of BAY 1753011, a Dual V1a/V2 Vasopressin Receptor Antagonist, in Patients with Congestive Heart Failure: AVANTI Study
    Um Ensaio Multicêntrico, Aleatorizado, de Grupos Paralelos, com Dupla Ocultação, Controlado com Substância Ativa e com Placebo de BAY 1753011, um Antagonista Duplo dos Recetores V1a/V2 da Vasopressina, em Doentes com Insuficiência Cardíaca Congestiva:
    Ensaio AVANTI
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    BAY 1753011 in Congestive Heart Failure
    BAY 1753011 na Insuficiência Cardíaca Congestiva
    A.3.2Name or abbreviated title of the trial where available
    AVANTI Study
    Estudo AVANTI
    A.4.1Sponsor's protocol code number17909
    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 SponsorBayer AG
    B.1.3.4CountryGermany
    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 supportBayer AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBayer AG
    B.5.2Functional name of contact pointBayer Clinical Trials Contact
    B.5.3 Address:
    B.5.3.1Street AddressMüllerstrasse 178
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code13342
    B.5.3.4CountryGermany
    B.5.4Telephone number+4930300139003
    B.5.6E-mailclinical-trials-contact@bayer.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 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 nameBAY 1753011 30mg
    D.3.2Product code BAY 1753011
    D.3.4Pharmaceutical form Coated tablet
    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 INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeBAY 1753011
    D.3.9.3Other descriptive nameBAY1753011
    D.3.9.4EV Substance CodeSUB177066
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 nameBAY 1753011 5mg
    D.3.2Product code BAY 1753011
    D.3.4Pharmaceutical form Coated tablet
    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 INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeBAY 1753011
    D.3.9.3Other descriptive nameBAY1753011
    D.3.9.4EV Substance CodeSUB177066
    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: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Furorese® 40 mg Tabletten
    D.2.1.1.2Name of the Marketing Authorisation holderHexal AG
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameFurorese® 40 mg Tabletten
    D.3.4Pharmaceutical form Tablet
    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 INNFUROSEMIDE
    D.3.9.1CAS number 54-31-9
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameFUROSEMIDE
    D.3.9.4EV Substance CodeSUB07849MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 placeboCoated tablet
    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 placeboCoated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    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
    Heart failure
    Insuficiência Cardíaca
    E.1.1.1Medical condition in easily understood language
    Heart failure
    Insuficiência Cardíaca
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10008908
    E.1.2Term Chronic heart failure
    E.1.2System Organ Class 100000004849
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of 30 mg of BAY 1753011, with or without furosemide, versus furosemide alone in patients with HF and objective evidence of congestion

    Avaliar a eficácia de 30 mg de BAY 1753011, com ou sem furosemida, versus furosemida isoladamente em doentes com IC e provas objetivas de congestão
    E.2.2Secondary objectives of the trial
    To assess the safety and pharmacodynamics of 30 mg of BAY 1753011, with or without furosemide, versus furosemide alone in patients with HF and objective evidence of congestion
    Avaliar a segurança e a farmacodinâmica de 30 mg de BAY 1753011, com ou sem furosemida, versus furosemida isoladamente em doentes com IC e provas objetivas de congestão
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent signed before any study-specific procedure.
    2. Ability to understand and follow study-related instructions as a documented decision of the investigator
    3. Men and women aged ≥ 18 years ≤ 85 years. Lower age limit may be higher if legally requested in the participating country.
    4. Men must agree to use condoms during sexual intercourse.
    5. Women can only be enrolled if of non-child bearing potential
    6. History of CHF (HF with reduced, preserved or mid-range EF) on individually optimized treatment with HF medications unless contraindicated or not tolerated, for at least 12 weeks prior to index hospitalization and in accordance with international guidelines.
    7. Subjects admitted to the hospital with a primary diagnosis of decompensated HF including symptoms and signs of fluid overload requiring IV diuretic therapy in the ER or any time between day 1-3 of hospital admission
    8. Subjects on an average/usual total daily dose of loop diuretic ≥ 40 mg of furosemide or equivalent, within 4 weeks prior to index
    hospitalization.
    AND
    9. At least one of the following 5 parameters any day between 3-7 of index hospitalization
    Ai. Drop in BNP or NT-proBNP ≤ 30% from admission values (if measured during index hospitalization) or
    Aii. BNP ≥ 500 pg/ml or NT-proBNP ≥ 1800 pg/ml at screening
    B. BW loss <0.4 kg per 40 mg furosemide at day 4 of index hospitalization
    C. CCS ≥ 3
    D. Hypervolemic hyponatremia defined as serum sodium < 136 mmol/l
    E. In hospital worsening renal function defined as increased serum creatinine ≥ 0.3 mg/dl compared to index hospitalization admission values
    AND at least one the following
    Ei. JVP ≥ 10 cm on physical examination
    Eii. IVC diameter > 21 mm
    Eiii. IVC collapse with sniff < 50%
    Eiv. At least 2+ peripheral edema or pulmonary edema or pleural effusion on chest X-ray or clinical exam
    1. Consentimento informado escrito assinado antes de qualquer procedimento específico do ensaio.
    2. Capacidade para entender e seguir as instruções do ensaio conforme avaliação do Investigador que deve documentar a sua decisão.
    3. Homens e mulheres com idade ≥ 18 anos e ≤ 85 anos. O limite inferior da idade poderá ser mais alto se legalmente exigido no país participante.
    4. Os homens têm de concordar em utilizar preservativo durante as relações sexuais.
    5. As mulheres só podem ser incluídas se não tiverem possibilidade de engravidar.
    6. História de ICC [IC com fração de ejeção (FE) reduzida, preservada ou média] a receber tratamento personalizado otimizado com medicamentos para a IC, exceto se estes forem contraindicados ou não tolerados, durante um período mínimo de 12 semanas antes da hospitalização inicial e de acordo com as orientações clínicas internacionais.
    7. Sujeitos admitidos no hospital com um diagnóstico primário de IC descompensada, incluindo sinais e sintomas de sobrecarga de fluidos, que precisem de receber terapêutica diurética IV no SU ou em qualquer momento entre os dias 1 e 3 a contar da data da hospitalização (hospitalização inicial).
    8.Sujeitos sob uma dose diária total média/habitual de diuréticos da ansa ≥ 40mg de Furosemida ou equivalente, nas 4 semanas anteriores à data da hospitalização inicial.
    E
    9. Presença de pelo menos um dos 5 parâmetros seguintes em qualquer momento entre os dias 3 e 7 a contar da data da hospitalização inicial (período de triagem)
    Ai. Redução ≤ 30% do BNP ou do NT-proBNP face aos valores iniciais no momento da admissão (se estes tiverem sido determinados durante a hospitalização inicial) ou
    Aii. BNP ≥ 500 pg/ml ou NT-proBNP ≥ 1800 pg/ml no momento da triagem (entre os dias 3 e 7 a contar da data da hospitalização inicial) 1,
    B. Redução do peso corporal (PC) < 0,4 kg por 40 mg de furosemida no dia 4 a contar da data da hospitalização inicial
    C. Índice de congestão composto (Composite congestion score, CCS) ≥ 3
    D. Hiponatremia hipervolémica definida como sódio sérico < 136 mmol/l
    E. Agravamento da função renal no hospital, definida como um aumento da creatinina sérica ≥ 0,3 mg/dl face aos valores iniciais no momento da hospitalização inicial E pelo menos um dos seguintes
    Ei. Pressão venosa jugular (PVJ) ≥ 10 cm detetada na avaliação física
    Eii. Diâmetro da veia cava inferior (VCI) > 21 mm
    Eiii. VCI com colapso inspiratório < 50%
    Eiv. Pelo menos 2 das seguintes condições: edema periférico ou edema pulmonar ou derrame pleural detetado por radiografia torácica ou na avaliação clínica
    E.4Principal exclusion criteria
    1. Body Mass Index (BMI) < 18.5 kg/m2 or > 35 kg/m2
    2. Known hypersensitivity to the study drugs
    3. Participation in another interventional clinical study or treatment with investigational medicinal product 30 days or five half-lives of the investigational drug prior to screening
    4. Any other condition or therapy that would make the subject unsuitable for this study and would not allow participation for the full planned study period in the judgment of the investigator (e.g. severe
    Chronic Obstructive Pulmonary Disease (COPD), Severe chronic infectious diseases [endocarditis, H.I.V, etc.])
    5. Malignancy or other non-cardiac condition limiting life expectancy to < 1 year, per physician judgment
    6. Known current alcohol and/or illicit drug abuse that may interfere with the subject’s safety and / or compliance at the discretion of the investigator
    7. Close affiliation with the investigational site or the sponsor; e.g., a close relative of the investigator or the sponsor or a dependent person (e.g., employee or student of the investigational site or the sponsor)
    8. Subject is in custody by order of an authority or a court of law
    9. Acute de-novo HF
    10. Active or history of acute inflammatory heart disease, within 3 months prior to screening, e.g., acute myocarditis
    11. Acute coronary syndrome, including unstable angina, NSTEMI or STEMI, or major CV surgery including CABG, PCI within 3 months prior to screening
    12. Implantation of a CRT device within 3 months prior to screening
    13. Stroke or carotid angioplasty within 3 months prior to screening
    14. History of heart transplant or need for urgent heart transplantation, or presence of left ventricular assist device
    15. Any primary cause of HF scheduled for surgery or interventional therapy (e.g., TAVI), e.g., valve disease such as severe aortic stenosis or mitral valve regurgitation
    16. Hemodynamically significant ventricular arrhythmias or therapeutic defibrillator shock within 4 weeks prior to screening
    17. Resting HR while awake of < 50 BPM or > 110 BPM (in case of AF > 120 BPM) at the time of screening or at randomization
    18. Symptomatic hypotension with systolic BP < 95 mmHg during screening or at randomization
    19. Any systolic BP < 85 mmHg during screening or at randomization
    20. Complex congenital heart disease
    21. Sepsis or ongoing systemic inflammation
    22. Hypertrophic obstructive or restrictive cardiomyopathy
    23. Requirement of mechanical support or ultrafiltration/hemodialysis
    24. Use of IV vasodilators or IV inotropic support within 24 hours prior to randomization or tolvaptan at any time during index hospitalization
    25. Estimated GFR of < 30 ml/min/1.73 m2 determined by the MDRD equation at screening
    26. Serum potassium ≥ 5.5 mmol/L or ≤ 3.3 mmol/L at screening
    27. Serum sodium ≥ 146 mmol/L or ≤ 130 mmol/L at screening
    28. Hepatic insufficiency classified as Child-Pugh B or C
    29. Syndrome of Inappropriate Antidiuretic Hormone Secretion
    30. Diabetes insipidus
    31. Thyroid disease requiring current treatment and/or (sub)clinical hyperthyroidism or hypothyroidism
    32. Concomitant treatment with potassium-sparing diuretic (with the exception of MRA) that cannot be stopped prior to randomization and for the duration of the treatment period
    33. Concomitant treatment with strong and moderate inducers or inhibitors of CYP3A4
    34. Concomitant treatment with probenecid
    1. Índice de Massa Corporal (IMC) < 18.5 kg/m2 ou > 35 kg/m2
    2. Hipersensibilidade conhecida aos medicamentos do ensaio (BAY 173011 e furosemida, ou algum dos excipientes)
    3. Participação noutro ensaio clínico intervencional ou tratamento com um medicamento experimental nos 30 dias, ou período correspondente a cinco semividas do medicamento experimental, anteriores à triagem
    4. Qualquer outra doença ou tratamento que torne o participante não adequado para este ensaio ou não permita a sua participação durante todo o período do ensaio, segundo o critério do investigador (ex. Doença Pulmonar Obstrutiva Crónica (DPOC) grave, doenças infeciosas crónicas graves [endocardite, H.I.V., etc])
    5. Doença maligna ou outra condição não cardíaca que limite a esperança de vida a um período < 1 ano, segundo o critério do médico
    6. Situação conhecida e atual de abuso de álcool e/ou drogas ilícitas que possa interferir com a segurança e/ou adesão ao tratamento, segundo o critério do investigador
    7. Ligação próxima com o centro de investigação ou o promotor; p. ex. um familiar próximo do investigador ou do promotor, ou uma pessoa dependente (tal como um empregado ou estudante do centro de investigação ou do promotor)
    8. Doente em custódia por decisão de uma autoridade ou de um tribunal
    9. IC aguda "de novo"
    10. Doença cardíaca inflamatória aguda ativa ou passada, nos 3 meses anteriores à triagem, p. ex. miocardite aguda
    11. Síndrome coronária aguda, incluindo angina instável, enfarte do miocárdio sem elevação do segmento ST (EMSEST) ou com elevação do segmento ST (EMCEST), ou cirurgia cardiovascular (CV) importante incluindo cirurgia de derivação (bypass) das artérias coronárias (CABG) e intervenção coronária percutânea (ICP), nos 3 meses anteriores à triagem
    12. Implantação de um dispositivo de terapia de ressincronização cardíaca (TRC) nos 3 meses anteriores à triagem
    13. Acidente vascular cerebral (AVC) ou angioplastia carotídea nos 3 meses anteriores à triagem
    14. Antecedentes de transplante cardíaco ou necessidade de transplante cardíaco urgente, ou presença de dispositivo de assistência ventricular esquerda
    15.Cirurgia programada ou terapia intervencional (p. ex. TAVI) para qualquer causa primária de IC, p. ex. doença valvular tal como estenose aórtica grave ou regurgitação da válvula mitral
    16. Arritmias ventriculares hemodinamicamente significativas ou tratamento de choque com desfibrilhador nas 4 semanas anteriores à triagem
    17. Frequência cardíaca (FC) em repouso do doente (acordado) < 50 batimentos/minuto (BPM) ou > 110 BPM (em caso de fibrilhação auricular > 120 BPM) no momento da triagem ou da aleatorização
    18. Hipotensão sintomática com pressão sistólica < 95 mm Hg durante o período de triagem ou no momento da aleatorização
    19. Qualquer medição de pressão sistólica < 85 mm Hg durante o período de triagem ou no momento da aleatorização
    20. Doença cardíaca congénita complexa
    21. Sépsis ou inflamação sistémica em curso (SIRS)
    22. Cardiomiopatia hipertrófica obstrutiva ou restritiva
    23. Necessidade de suporte mecânico (bomba de balão intra-aórtico, intubação endotraqueal, ventilação mecânica ou dispositivo de assistência ventricular) ou ultrafiltração/hemodiálise
    24. Utilização de vasodilatadores (p. ex. nitratos) intravenosos (IV) ou suporte inotrópico IV nas 24 horas anteriores à aleatorização ou utilização de tolvaptano em qualquer momento desta hospitalização
    25. Taxa de filtração glomerular estimada < 30 ml/min/1,73 m2 determinada através da equação Modified Diet and Renal Disease no momento da triagem; reavaliações permitidas conforme clinicamente necessárias
    26. Potássio sérico ≥ 5,5 mmol/l ou ≤ 3,3 mmol/l no momento da triagem; reavaliações permitidas conforme clinicamente necessárias
    27. Sódio sérico ≥ 146 mmol/l ou ≤ 130 mmol/l no momento da triagem; reavaliações permitidas conforme clinicamente necessárias
    28. Insuficiência hepática classificada como Child-Pugh B ou C
    29. Síndrome de secreção inadequada de hormona antidiurética (SIADH)
    30. Diabetes insipidus
    31. Doença da tiroide com necessidade de tratamento e/ou hipertiroidismo ou hipotiroidismo (sub)clínico no momento presente
    32. Tratamento concomitante com diuréticos poupadores de potássio [à exceção de antagonistas dos recetores mineralocorticoides (MRA)] que não possa ser interrompido antes da aleatorização e durante todo o período de tratamento
    33. Tratamento concomitante com indutores fortes ou moderados ou inibidores do CYP3A4 (será disponibilizada uma lista de medicamentos concomitantes proibidos ao investigador)
    34. Tratamento concomitante com probenecid
    E.5 End points
    E.5.1Primary end point(s)
    PART A: Change in body weight and serum creatinine (Day 1 vs. Day 30)

    PART B: Change in body weight and BUN/creatinine ratio (Day 30 vs. Day 60)
    PARTE A: Alteração do peso corporal e da creatinina sérica (Dia 1 vs. Dia 30)
    PARTE B: Alteração do peso corporal e Razão Azoto Ureico no sangue/creatinina (Dia 30 vs. Dia 60)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 30 and day 60
    Dia 30 e dia 60
    E.5.2Secondary end point(s)
    • Safety by TEAE reporting (including SAE)
    • Pharmacodynamics by change in augmentation index
    • Segurança através de notificação dos efeitos adversos emergentes do tratamento (EAET)
    • Farmacodinâmica através da alteração do índice de aumento
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 30 and day 60
    Dia 30 e dia 60
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarkers and Quality of Life
    Biomarcadores e Qualidade de Vida
    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) No
    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) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA65
    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
    Austria
    Bulgaria
    Greece
    Hungary
    Israel
    Italy
    Poland
    Portugal
    Spain
    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
    Última Visita do Último Participante
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    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: 104
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 310
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state49
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 384
    F.4.2.2In the whole clinical trial 414
    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)
    After completion of the study the patient will be treated with approved/available standard of care therapy as outlined in the international guidelines
    Após terminar o ensaio, o doente será tratado com o tratamento habitual aprovado/disponível como é indicado nas orientações internacionais
    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 Decision2019-04-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-04-29
    P. End of Trial
    P.End of Trial StatusOngoing
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