E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension
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Hipertension arterial pulmonar |
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E.1.1.1 | Medical condition in easily understood language |
Pulmonary Arterial Hypertension is a condition in which the pressure in the blood vessels going to the lungs (the pulmonary arteries) is higher than normal |
La hipertensión arterial pulmonar es una condición en la que la presión en los vasos sanguíneos que van a los pulmones (las arterias pulmonares) es más alta de lo normal |
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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 | 16.1 |
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 |
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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 assess the long-term safety of macitentan in patients with pulmonary arterial hypertension (PAH) beyond treatment in the AC-055-310 study. |
Valorar la seguridad a largo plazo de macitentan en pacientes con hipertensión arterial pulmonar (HAP) posterior al tratamiento en el estudio AC-055-310. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Signed informed consent prior to any study-mandated procedure.
? Patients with PAH who completed the ORCHESTRA study (AC-055-310) as scheduled.
? Women of childbearing potential must:
? have a negative serum pregnancy test at Visit 1 (i.e., Visit 4 of study AC-055-310) and agree to perform monthly serum pregnancy tests.
? agree to use two reliable methods of contraception in parallel, from Visit 1 until 1 month after study drug discontinuation. |
• Consentimiento informado firmado en anterioridad de cualquier procedimiento exigido por el estudio.
• Pacientes con HAP que finalizaron el estudio ORCHESTRA (AC-055-310) tal como previsto.
• Las mujeres en edad fértil deben:
– presentar una prueba de embarazo en suero negativa en la visita 1 (es decir, la visita 4 del estudio AC-055-310) y estar de acuerdo en que se les realicen pruebas de embarazo en suero mensualmente.
– aceptar utilizar en paralelo dos métodos anticonceptivos fiables, a partir de la visita 1 hasta 1 mes después de la discontinuación del medicamento del estudio.
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E.4 | Principal exclusion criteria |
? Patients who prematurely discontinued study drug in the ORCHESTRA study (AC-055-310).
? Females who are lactating or pregnant (positive Visit 1 pregnancy test) or plan to become pregnant during the study.
? Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN). |
• Pacientes que discontinuaron prematuramente el medicamento del estudio en el estudio ORCHESTRA (AC-055-310).
• Mujeres durante la lactancia o embarazadas (prueba de embarazo positiva en la visita 1) o con plan de quedarse embarazadas durante el estudio.
• Aspartato aminotransferasa (AST) y/o alanino aminotransferasa (ALT) 3 veces el límite superior de la normalidad (LSN).
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints
? Treatment-emergent adverse events (AEs)1
? AEs leading to premature discontinuation of study drug
? Treatment-emergent serious adverse events (SAEs)
? Proportion of patients with treatment-emergent ALT and/or AST abnormality (> 3, > 5, and > 8 × ULN) associated or not with total bilirubin > 2 × ULN, up to EOT.
? Proportion of patients with treatment-emergent hemoglobin abnormality (? 100 g/L, and ? 80 g/L), up to EOT. |
Criterios de valoración de seguridad
• Acontecimientos adversos emergentes del tratamiento (AA)
• AA que resultan en la discontinuación prematura del medicamento del estudio
• Acontecimientos adversos graves emergentes del tratamiento (AAG)
• Proporción de pacientes con anomalías de ALT y/o AST emergentes del tratamiento ( 3, 5, y 8 LSN) asociadas o no con valores de bilirrubina total 2 LSN, hasta el EOT.
• Proporción de pacientes con anomalías de hemoglobina emergentes del tratamiento ( 100 g/l y 80 g/l), hasta el EOT.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monthly laboratory test and 6-Monthly visit |
Prueba de laboratorio mensuales y visita cada 6 meses |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |