E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension (PAH) |
Hipertensión arterial pulmonar (HAP) |
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E.1.1.1 | Medical condition in easily understood language |
Hypertension in the artery leading from the right heart to the lungs |
Hipertensión en la arteria principal que va desde el lado derecho del corazón a los pulmones |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effect on pulmonary vascular resistance (PVR) of an initial triple oral regimen (macitentan, tadalafil, selexipag) versus an initial dual oral regimen (macitentan, tadalafil, placebo) in newly diagnosed, treatment-naïve subjects with pulmonary arterial hypertension (PAH). |
Comparar el efecto en la resistencia vascular pulmonar (RVP) de un esquema oral inicial triple (macitentán, tadalafilo, selexipag) frente a un esquema oral inicial doble (macitentán, tadalafilo, placebo) en sujetos con hipertensión arterial pulmonar (HAP) recién diagnosticada y sin tratamiento previo. |
|
E.2.2 | Secondary objectives of the trial |
To compare an initial triple oral regimen (macitentan, tadalafil, selexipag) with an initial dual oral regimen (macitentan, tadalafil, placebo) in newly diagnosed, treatment-naïve subjects with PAH, with respect to cardio-pulmonary hemodynamics (other than PVR), exercise capacity, disease severity, morbidity/mortality, safety, and tolerability. |
Comparar un esquema oral inicial triple (macitentán, tadalafilo, selexipag) con un esquema oral inicial doble (macitentán, tadalafilo, placebo) en sujetos con HAP recién diagnosticada y sin tratamiento previo, con respecto a la hemodinámica cardiopulmonar (excepto la RVP), la capacidad de ejercicio, la gravedad de la enfermedad, los acontecimientos de progresión de la enfermedad, la seguridad y la tolerabilidad. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent prior to any study-mandated procedure. - Initial PAH diagnosis < 6 months prior to enrollment. - RHC performed between Day −28 and Day 1, meeting all the following criteria: • Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg. • Pulmonary artery wedge pressure or left ventricular end-diastolic pressure ≤ 15 mmHg. • PVR ≥ 480 dyn•sec/cm5 (≥ 6 Wood Units). • Negative vasoreactivity test mandatory in idiopathic, heritable, and drug/toxin induced PAH (at this or a previous RHC). - Symptomatic PAH belonging to one of the following subgroups: • Idiopathic. • Heritable. • Drug or toxin induced. • Associated with one of the following: Connective tissue disease; HIV infection; Congenital heart disease. - 6-minute walk distance (6MWD) ≥ 50 m at screening. - Women of childbearing potential must not be pregnant, must perform regular pregnancy tests, and use reliable contraception. |
- Consentimiento informado firmado antes de realizar algún procedimiento requerido por el estudio. - Diagnóstico inicial de HAP <6 meses antes del día 1. - CCD realizado entre el día −28 y el día 1, que reúne todos los criterios siguientes: • Presión arterial pulmonar media (PAPm) ≥25 mmHg. • Presión de enclavamiento de la arteria pulmonar o presión telediastólica del ventrículo izquierdo ≤15 mmHg. • RVP ≥480 dyn·seg/cm5 (≥6 unidades de Wood). • Es obligatorio un resultado negativo en la prueba de vasorreactividad en caso de HAP idiopática, congénita e inducida por medicamentos/toxinas (en este CCD o en uno previo). - HAP sintomática de uno de los siguientes subgrupos: • Idiopática. • Congénita. • Inducida por medicamentos o toxinas. • Asociada a: enfermedad del tejido conjuntivo, infección por VIH, enfermedad cardiaca congénita. - Distancia en la prueba de marcha de 6 minutos (6MWD) ≥50 m en la selección. - Las mujeres que pueden quedarse embarazadas deben no quedarse embarazadas, deben realizarse de forma regular pruebas de embarazo, y utilizar anticonceptivos eficaces. |
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E.4 | Principal exclusion criteria |
- Any PAH-specific drug therapy at any time. |
- Cualquier tratamiento farmacológico específico para la HAP en cualquier momento. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Pulmonary vascular resistance |
Resistencia vascular pulmonar |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to Week 26 |
Desde la visita basal hasta la semana 26 |
|
E.5.2 | Secondary end point(s) |
N-terminal pro B-type natriuretic peptide (NT-proBNP), 6-minute walk distance, WHO Functional Class, cardiac hemodynamics as assessed by right heart catheterization, time from randomization to the first disease progression event |
Prohormona N-terminal del péptido natriurético tipo B (NT-proBNP), distancia en la prueba de marcha de 6 minutos, clase funcional de la OMS, hemodinámica cardiaca evaluada por cateterismo cardiaco derecho, tiempo desde la aleatorización hasta el primer acontecimiento de progresión de la enfermedad |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to Week 26. For time to the first disease progression event, baseline to 26 weeks after last patient enrolled. |
Desde la visita basal hasta la semana 26. Para el primer acontecimiento de progresión de la enfermedad, desde la visita basal hasta la semana 26 después de la inclusión del último sujeto. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Denmark |
France |
Germany |
Ireland |
Italy |
Netherlands |
Norway |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |