E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Arterial Hypertension |
Ipertensione Arteriosa Polmonare |
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E.1.1.1 | Medical condition in easily understood language |
Pulmonary Arterial Hypertension is an increase in blood pressure in the pulmonary arteries leading to shortness of breath, dizziness, fainting and other symptoms. |
L`ipertensione arteriosa polmonare e' l`aumento della pressione sanguigna nelle arterie polmonari che determina sintomi quali fiato corto, capogiri, stanchezza e altri |
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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 | 14.1 |
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 demonstrate the effect of ACT-293987 on time to first clinical worsening in patients with pulmonary arterial hypertension (PAH). |
- Dimostrare lâÂÂeffetto di ACT-293987 sul tempo di insorgenza del primo evento di peggioramento clinico nei pazienti con Ipertensione Arteriosa Polmonare (PAH) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of ACT-293987 on exercise capacity and other secondary and exploratory efficacy endpoints in patients with PAH; - To evaluate the safety and tolerability of ACT-293987 in patients with PAH. |
- Valutare l'effetto di ACT-293987 sulla capacita' di esercizio fisico e altri endpoints secondari ed esplorativi di efficacia nei pazienti con PAH; - Valutare la sicurezza e la tollerabilita' di ACT-293987 nei pazienti con PAH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent prior to initiation of any study-mandated procedure; - Male and female patients aged from 18 years to 75 years inclusive with symptomatic AH; - Documented hemodynamic diagnosis of PAH. |
- Consenso informato firmato prima di iniziare qualsiasi procedura prevista dallo studio; - Uomini e donne di eta' compresa tra 18 anni e i 75 anni (18 < eta' < 75) con PAH sintomatica; - Diagnosi emodinamica di PAH clinicamente documentata. |
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E.4 | Principal exclusion criteria |
- Patients who have received prostacyclin (epoprostenol) or prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) within 1 month before Baseline Visit, or are scheduled to receive any of these compounds during the trial. - Patients with moderate or severe obstructive lung disease. - Patients with moderate or severe restrictive lung disease. - Patients with moderate or severe hepatic impairment (Child-Pugh B and C). - Patients with documented left ventricular dysfunction. - Patients with severe renal insufficiency. - Patients with BMI <18.5 Kg/ m2 |
- Pazienti che hanno assunto prostaciclina (epoprostenolo) o analoghi delle prostaciclina (cioe' treprostinile, iloprost, beraprost) entro 1 mese prima della Visita di Baseline, o che hanno in programma di assumere uno di questi farmaci nel corso dello studio; - Pazienti con pneumopatia ostruttiva moderata o grave; - Pazienti con pneumopatia restrittiva moderata o grave; - Pazienti con danno epatico moderato o grave (Child-Pugh classe B e C; - Pazienti con disfunzione ventricolare sinistra clinicamente documentata; - Pazienti con insufficienza renale grave; - Pazienti con BMI < 18,5kg/m2. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first clinical worsening up to 7 days after last study drug intake defined as: - Death (all-cause mortality) - Hospitalization for worsening of PAH - Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy - Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to worsening of PAH. Disease progression Clinical worsening will be adjudicated by an independent Critical Event Committee. |
Tempo di insorgenza del primo evento di peggioramento clinico fino a 7 giorni dopo lâÂÂassunzione dellâÂÂultima dose di farmaco in studio, definito come: - Morte (per tutte le cause di mortalita`) - Ospedalizzazione per peggioramento della PAH - Peggioramento della PAH che comporti un trapianto di polmone o settostomia atriale con palloncino - Peggioramento della PAH che comporti lâÂÂinizio di terapia con prostanoidi per via parenterale e o di ossigeno terapia cronica - Progressione della malattia. Il peggioramento clinico sara` giudicato da un comitato indipendente, il Critical Event Committee (CEC). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
It is an event-driven trial |
Questa e' una sperimentazione clinica evento-guidata |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability |
tollerabilita' |
|
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Argentina |
Australia |
Belarus |
Canada |
Chile |
China |
Colombia |
India |
Israel |
Korea, Republic of |
Malaysia |
Mexico |
Peru |
Russian Federation |
Singapore |
Switzerland |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
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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
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End of Study will coincide with Study Closure (if no premature drug discontinuation) |
La conclusione della sperimentazione coincidera' con la chiusura dello studio (in caso di non prematura interruzione) |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 45 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 45 |
E.8.9.2 | In all countries concerned by the trial days | 0 |