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    Summary
    EudraCT Number:2019-004131-24
    Sponsor's Protocol Code Number:67896062CTP3001
    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:2020-07-20
    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 number2019-004131-24
    A.3Full title of the trial
    A prospective, randomized, double-blind, multicenter, placebo-controlled, parallel group, adaptive Phase 3 study with open-label extension to evaluate efficacy and safety of macitentan 75 mg in inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension.

    Macitentan in inoperAble or persistent/reCurrent chronIc ThromboEmbolic Pulmonary Hypertension (MACiTEPH)
    Estudio en fase III, prospectivo, aleatorizado, doble ciego, multicéntrico, controlado con placebo, de grupos paralelos y flexible con ampliación abierta para evaluar la eficacia y la seguridad de macitentán 75 mg en la hipertensión pulmonar tromboembólica crónica inoperable o persistente/recurrente.

    Macitentán en la hipertensión pulmonar tromboembólica crónica inoperable o persistente/recurrente (MACiTEPH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 study to evaluate whether macitentan 75 mg is an effective and safe treatment for patients with inoperable or persistent chronic thromboembolic pulmonary hypertension.
    Estudio en fase III para evaluar si macitentán 75 mg es un tratamiento seguro y efectivo para pacientes con hipertensión pulmonar tromboembólica crónica inoperable o persistente/recurrente.
    A.3.2Name or abbreviated title of the trial where available
    MACiTEPH
    MACiTEPH
    A.4.1Sponsor's protocol code number67896062CTP3001
    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 SponsorACTELION Pharmaceuticals Ltd.
    B.1.3.4CountrySwitzerland
    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 supportActelion Pharmaceuticals Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag, S.A
    B.5.2Functional name of contact pointGlobal Clinical Operations
    B.5.3 Address:
    B.5.3.1Street AddressPaseo de las Doce Estrellas, 5-7
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28042
    B.5.3.4CountrySpain
    B.5.4Telephone number+34917228696
    B.5.5Fax number+34917228624
    B.5.6E-mailLGuardia@its.jnj.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 Opsumit®
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    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 nameMacitentan tablets
    D.3.2Product code JNJ-67896062 / ACT-064992
    D.3.4Pharmaceutical form Film-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 INNMACITENTAN
    D.3.9.1CAS number 441798-33-0
    D.3.9.2Current sponsor codeJNJ-67896062-AAA
    D.3.9.3Other descriptive nameACT-064992
    D.3.9.4EV Substance CodeSUB89247
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(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.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 nameMacitentan tablets
    D.3.2Product code JNJ-67896062 / ACT-064992
    D.3.4Pharmaceutical form Film-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 INNMACITENTAN
    D.3.9.1CAS number 441798-33-0
    D.3.9.2Current sponsor codeJNJ-67896062-AAA
    D.3.9.3Other descriptive nameACT-064992
    D.3.9.4EV Substance CodeSUB89247
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 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 nameMacitentan tablets
    D.3.2Product code JNJ-67896062 / ACT-064992
    D.3.4Pharmaceutical form Film-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 INNMACITENTAN
    D.3.9.1CAS number 441798-33-0
    D.3.9.2Current sponsor codeJNJ-67896062-AAA
    D.3.9.3Other descriptive nameACT-064992
    D.3.9.4EV Substance CodeSUB89247
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number37.5
    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 placeboFilm-coated 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 placeboFilm-coated 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 placeboFilm-coated tablet
    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
    Chronic thromboembolic pulmonary hypertension
    Hipertensión pulmonar tromboembólica crónica
    E.1.1.1Medical condition in easily understood language
    CTEPH is a rare type of pulmonary hypertension, a condition in which the pressure in the blood vessels going to the lungs (pulmonary arteries) is higher than normal due to restricted blood flow.
    HPTEC es un tipo raro de HP, una condición en la cual la presión en los vasos sanguíneos que van a los pulmones (arterias pulmonares) es más alta de lo normal debido al flujo sanguíneo restringido.
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10064911
    E.1.2Term Pulmonary arterial hypertension
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH).
    Evaluar el efecto de macitentán 75 mg en comparación con el placebo en la capacidad para hacer ejercicio en la semana 28 en pacientes con hipertensión pulmonar tromboembólica crónica (HPTEC).
    E.2.2Secondary objectives of the trial
    • To evaluate the effect of macitentan 75 mg versus placebo on time to clinical worsening up to Week 52.
    • To evaluate the effect of macitentan 75 mg versus placebo on WHO FC at Week 28.
    • To evaluate the effect of macitentan 75 mg versus placebo on quality of life at Week 28.
    • To evaluate the effect of macitentan 75 mg versus placebo on daily physical activity.
    • Evaluar el efecto de macitentán 75 mg en comparación con el placebo en el tiempo hasta el empeoramiento clínico hasta la semana 52.
    • Evaluar el efecto de macitentán 75 mg en comparación con el placebo en la CF de la OMS en la semana 28
    •Evaluar el efecto de macitentán 75 mg en comparación con el placebo en la calidad de vida en la semana 28
    • Evaluar el efecto de macitentán 75 mg en la actividad física diaria.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    • The objective of this sub-study is to confirm the effect of macitentan 75 mg versus placebo on PVR in participants with inoperable or persistent/recurrent CTEPH.
    • Patients participating in the substudy will undergo RHC at Screening and at Week 28.
    • The RHC will only be performed at sites able to comply with the protocol-specific RHC guidelines.
    • El objetivo de este subestudio es confirmar el efecto de macitentan 75 mg versus placebo en PVR en participantes con HPTEC inoperable o persistente/recurrente.
    • Los pacientes que participan en el subestudio se someterán a CCD en la evaluación y en la semana 28.
    • El CCD solo se realizará en aquellos centros que puedan cumplir con las pautas de CCD específicas del protocolo.
    E.3Principal inclusion criteria
    • Male or female ≥ 18 and ≤80 years of age.
    • CTEPH (WHO Group 4) fulfilling one of the following criteria:
    a. Inoperable due to the localization of the obstruction being surgically inaccessible (ie, distal disease) as confirmed by the adjudication committee (AC), and diagnosed based on
    • At least 2 of the following assessments in the 14 month-period prior to Randomization: Ventilation / Perfusion (V/Q) scan, pulmonary angiography (PA), computed tomography pulmonary angiogram (CTPA), magnetic resonance angiography (MRA).
    - RHC at least 12 weeks after full anticoagulation showing the following (at Screening or in the 24 week period prior to Randomization): mPAP > 20 mmHg, PAWP ≤15 mmHg and PVR ≥240 dyn·sec/cm5.
    b. Persistent/recurrent CTEPH after BPA, and deemed inoperable due to the localization of the obstruction being surgically inaccessible (ie, distal disease) as confirmed by the AC, diagnosed based on:
    • At least one of the following assessments performed after the latest BPA in the 14-month period prior to Randomization: V/Q scan, PA, CTPA or MRA
    • RHC at least 12 weeks after BPA and full anticoagulation showing the following (at Screening or in the 24-week period prior to Randomization): mPAP > 20 mmHg, PAWP ≤15 mmHg and PVR≥240 dyn·sec/cm5.
    c. Persistent/recurrent CTEPH after PEA (including PEA followed by BPA), diagnosed based on:
    • At least one of the following assessments performed after the PEA (and latest BPA following PEA, if applicable) in the 14-month period prior to Randomization: V/Q scan, PA, CTPA or MRA.
    • RHC performed at least 12 weeks after PEA (or latest BPA, if applicable) and full anticoagulationa showing the following (at Screening or in the 24 week period prior to Randomization): mPAP > 20 mmHg, PAWP ≤15 mmHg and PVR≥240 dyn·sec/cm5.
    • 6MWD ≥ 100 m AND ≤ 450 m, documented by an eligibility and a baseline 6MWT. The baseline 6MWD must not differ by more than 15% from the eligibility test.
    • WHO FC ≥II.
    • Varón o mujer ≥18 y ≤80 años de edad.
    • HPTEC (grupo 4 de la OMS) que cumple uno de los siguientes criterios:
    a. Inoperable debido a que la localización de la obstrucción es quirúrgicamente inaccesible (es decir, enfermedad distal) según lo confirmado por el comité de adjudicación (CA) y diagnosticada con base en:
    • Al menos 2 de las siguientes evaluaciones en los 14 meses anteriores a la aleatorización: Gammagrafía de ventilación/perfusión (GVP), angiografía pulmonar (AP), angiografía pulmonar por tomografía computarizada (APTC), angiografía por resonancia magnética (ARM).
    -CCD al menos 12 semanas después de la anticoagulación completaa que muestra lo siguiente (en la selección o en el periodo de 24 semanas antes de la aleatorización): -PAPm >20 mmHg Presión en cuña de la arteria pulmonar (PCAP) ≤15 mmHg o, si no está disponible o no es fiable, una presión diastólica final del ventrículo izquierdo (PDFVI) ≤15 mmHg - RVP en reposo 240 dyn-s/cm5
    b HPTEC persistente/recurrente después de una APB y considerada inoperable debido a que la localización de la obstrucción es inaccesible quirúrgicamente (es decir, enfermedad distal) según lo confirmado por el CA, diagnosticada con base en:
    • Al menos una de las siguientes evaluaciones realizadas después de la última APB en el periodo de 14 meses previo a la aleatorización: GVP, AP, APTC o ARM
    • CCD al menos 12 semanas después de la APB y la anticoagulación completaa que muestra lo siguiente (en la selección o en el periodo de 24 semanas antes de la aleatorización): -PAPm >20 mmHg -PCAP ≤15 mmHg o, si no está disponible o no es fiable, una PDFVI ≤15 mmHg
    -RVP 240 dyn-s/cm5
    c. HPTEC persistente/recurrente después de una EAP (incluida EAP seguida de APB), diagnosticada con base en:
    • Al menos una de las siguientes evaluaciones realizadas después de la EAP (y la última APB después de la EAP, si procede) en el periodo de 14 meses previo a la aleatorización: GVP, AP, APTC o ARM
    • CCD realizado al menos 12 semanas después de la EAP (o la última APB, si procede) y la anticoagulación completaa que muestra lo siguiente (en la selección o en el periodo de 24 semanas antes de la aleatorización):-PAPm >20 mmHg -PCAP ≤15 mmHg o, si no está disponible o no es fiable, una PDFVI ≤15 mmHg -RVP 240 dyn-s/cm5
    • DM6M ≥100 m Y ≤450 m, documentada por una elegibilidad y una PM6M de referencia. La DM6M de referencia no debe diferir en más del 15 % de la prueba de elegibilidad.
    • CF de la OMS ≥II
    E.4Principal exclusion criteria
    • Acute pulmonary embolism within 6 months prior to or during Screening.
    • Planned (during the double-blind period of the study) BPA.
    • Significant obstructive and restrictive lung disease.
    • Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements, in particular with 6MWT (eg, intermittent claudication).
    • Symptomatic coronary artery disease requiring an intervention within 3 months prior to or during Screening or anticipated during the DB period of the study.
    • Decompensated cardiac failure if not under close supervision.
    • Known and documented life-threatening cardiac arrhythmias.
    • Acute myocardial infarction within 6 months prior to, or during Screening.
    • Cerebrovascular events (including transient ischemic attack) within 3 months prior to, or during Screening.
    • Known or suspicion of pulmonary veno-occlusive disease (PVOD).
    • Administration of ERAs, intravenous, inhaled or subcutaneous prostacyclins / prostacyclin analogs, or investigational treatment within 90 days prior to Randomization.
    • Administration of riociguat within 90 days prior to Randomization (if its use as background medication becomes permissible based on pharmacokinetic DDI data during the conduct of the study, this exclusion criterion will no longer apply).
    • Change in dose or initiation of PDE-5 inhibitors, oral prostacyclins / prostacyclin analogues, prostacyclin receptor agonists (or riociguat, if its use becomes permissible during the study) within 90 days prior to Randomization, or anticipated during the 52-week DB period.
    • Hypotension, ie, systolic blood pressure (SBP) <90 mmHg or diastolic blood pressure (DBP) <50 mmHg at Screening.
    • Severe renal dysfunction with an estimated Glomerular Filtration Rate <30 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration formula at Screening.
    • Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, based on records that confirm documented medical history.
    • Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥1.5 the upper limit of normal (ULN) at Screening.
    • Hemoglobin 100 g/L (<10 g/dL) at Screening.
    • Embolia pulmonar aguda en los 6 meses anteriores a la fase de selección o durante dicha fase.
    • APB programada (durante el periodo doble ciego del estudio).
    • Enfermedad pulmonar obstructiva y restrictiva significativa
    • Afecciones agudas o crónicas (distintas de la disnea) que limitan la capacidad de cumplir con los requisitos del estudio, en particular con la PM6M (p. ej., claudicación intermitente).
    • Arteriopatía coronaria sintomática que requiere intervención (p. ej., intervención coronaria percutánea, cirugía de bypass de la arteria coronaria) en los 3 meses anteriores a la fase de selección o durante dicha fase o prevista durante el periodo DC del estudio
    • Insuficiencia cardíaca descompensada no supervisada estrechamente
    • Arritmias cardíacas potencialmente mortales conocidas y documentadas.
    • Infarto agudo de miocardio en los 6 meses anteriores a la fase de selección o durante dicha fase.
    • Acontecimientos cerebrovasculares (incluido ataque isquémico transitorio) en los 3 meses anteriores a la fase de selección o durante dicha fase.
    • Conocimiento o sospecha de enfermedad venooclusiva pulmonar (EVOP).
    • Administración de ARE, prostaciclinas/análogos de prostaciclina por vía intravenosa, inhalada o subcutánea, o tratamiento en investigación en los 90 días previos a la aleatorización.
    • Administración de riociguat en los 90 días previos a la aleatorización (si su uso como medicamento de base está permitido según los datos farmacocinéticos de IF durante la realización del estudio, este criterio de exclusión ya no se aplicará
    • Cambio en la dosis o inicio del uso de inhibidores de FDE-5, prostaciclinas/análogos de prostaciclina por vía oral, agonistas del receptor de prostaciclina (o riociguat, si su uso se permite durante el estudio) en los 90 días previos a la aleatorización, o previsto durante el periodo DC de 52 semanas.
    • Hipotensión, es decir, presión arterial sistólica (PAS) <90 mmHg o presión arterial diastólica (PAD) <50 mmHg en la selección.
    • Disfunción renal grave con una tasa de filtración glomerular estimada <30 ml/min/1,73 m2 utilizando la fórmula del grupo Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) en la selección.
    • Insuficiencia hepática de moderada a grave conocida, definida como clasificación B o C de Child-Pugh, según los registros que confirman la historia clínica documentada.
    • Aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) en suero ≥1,5 el límite superior de la normalidad (LSN) en la selección
    • Hemoglobina 100 g/l (<10 g/dl) en la selección.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline to Week 28 in exercise capacity (6-minute walk distance [6MWD], as measured by the 6-minute walk test [6MWT]).
    Cambio desde el momento de referencia hasta la semana 28 en la capacidad para hacer ejercicio (distancia de marcha de 6 minutos [DM6M], medida por la prueba de marcha de 6 minutos [PM6M]).
    E.5.1.1Timepoint(s) of evaluation of this end point
    From baseline to Week 28.
    Desde la visita basal a la semana 28
    E.5.2Secondary end point(s)
    • Clinical event committee (CEC) confirmed clinical worsening up to Week 52.
    • Improvement in WHO FC from baseline to Week 28.
    • Change from baseline to Week 28 in
    • Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®)
    − Cardiopulmonary symptom domain score
    − Cardiovascular symptom domain score
    • Euro Quality of life-5-Dimension-5-Level (EQ-5D-5L©) utility score.
    • Change from baseline to Week 28 in accelerometer-assessed proportion of time spent in moderate to vigorous physical activity.
    • El Comité de acontecimientos clínicos (CAC) confirmó empeoramiento clínico hasta la semana 52.
    • Mejora de la CF de la OMS desde el momento de referencia hasta la semana 28.
    • Cambio desde el momento de referencia hasta la semana 28 en:
    • Hipertensión arterial pulmonar: síntomas e impacto (PAH-SYMPACT®)
    - Puntuación del dominio de síntomas cardiopulmonares
    - Puntuación del dominio de síntomas cardiovasculares
    • Puntuación de utilidad del cuestionario europeo sobre calidad de vida de 5 niveles y 5 dimensiones (EQ-5D-5L©)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 28 and Week 52.
    Semana 28 y semana 52
    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 No
    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 Yes
    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) 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    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
    Argentina
    Australia
    Austria
    Bulgaria
    Canada
    China
    Colombia
    Czech Republic
    Germany
    Hungary
    Israel
    Italy
    Japan
    Korea, Republic of
    Lithuania
    Mexico
    Poland
    Romania
    Russian Federation
    Saudi Arabia
    Serbia
    Singapore
    Slovakia
    Spain
    Taiwan
    Turkey
    Ukraine
    United Arab Emirates
    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
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    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: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 150
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 95
    F.4.2.2In the whole clinical trial 230
    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)
    The options with the patients will be discussed after the end of OL phase.
    Las opciones con los pacientes se discutirán después del final de la fase abierta
    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 Decision2020-06-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-21
    P. End of Trial
    P.End of Trial StatusOngoing
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