E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The intended indication is Pulmonary Arterial Hypertension |
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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. |
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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 morbidity and mortality (MM) event in patients with pulmonary arterial hypertension (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. |
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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 PAH. - Documented hemodynamic diagnosis of PAH. |
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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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first CEC-confirmed Morbidity and mortality event (MM), 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
MM events will be adjudicated in a blinded fashion by an independent Critical Event Committee. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
It's an event-driven trial. |
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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 | 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 |
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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 | 3 |
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 |
Austria |
Belarus |
Belgium |
Canada |
Chile |
China |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Hungary |
India |
Ireland |
Israel |
Italy |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
Peru |
Poland |
Romania |
Russian Federation |
Serbia |
Singapore |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
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) |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |