E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Arterial Hypertension |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037405 |
E.1.2 | Term | Pulmonary hypertension primary |
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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 that ACT-064992 prolongs the time to thefirst morbidity or mortality event in patients with symptomatic pulmonary arterial hypertension. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the effect of ACT-064992 on exercisecapacity in patients with symptomatic pulmonary arterialhypertension.To evaluate the safety and tolerability of ACT-064992 inpatients with symptomatic pulmonary arterial hypertension. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOECONOMIA QUALITA DELLA VITA
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E.3 | Principal inclusion criteria |
Signed informed consent prior to initiation of any study mandated procedure.Patients with symptomatic pulmonary arterial hypertension (PAH) in modified WHO functional class II to IV.Patients with the following types of PAH belonging to groups 1.1 to 1.3 of the Venice classification:a. Idiopathic (IPAH); b. Familial (FPAH); or c. Related to: i. Collagen vascular disease;ii. Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair;iii. HIV infection; oriv. Drugs and toxins.PAH diagnosis confirmed by hemodynamic evaluation performed prior to randomization and showing all of the following: a. Mean pulmonary artery pressure (mPAP) = 25 mmHg at rest,b. Pulmonary capillary wedge pressure (PCWP) or leftventricular end diastolic pressure (LVEDP) < 15 mmHg,andc. Pulmonary vascular resistance (PVR) at rest= 240 dyn·sec/cm5. |
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E.4 | Principal exclusion criteria |
PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gauchers disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy.PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected.PAH Associated with significant venous or capillaryinvolvement (PCWP > 15 mmHg), Pulmonary veno-occlusive disease and Pulmonary capillary hemangiomatosis.Persistent pulmonary hypertension of the newborn.Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification.Pulmonary hypertension associated with moderate to severe obstructive lung disease: forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 65% of predicted value after bronchodilator administration.Pulmonary hypertension associated with moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value.Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal.Hemoglobin < 75% of the lower limit of the normal range.Systolic blood pressure < 100 mmHg.Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.Pregnant or breast-feeding.Known concomitant life-threatening disease with a lifeexpectancy < 12 months.Body weight < 40 kg.Any condition that prevents compliance with the protocol or adherence to therapy.Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise.Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.Systemic treatment within 1 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mTOR inhibitors).Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from baseline to first morbidity or mortality event, defined as follows:1. Death, or2. Atrial septostomy, or3. Lung transplantation, or4. Initiation of intravenous or subcutaneous prostanoids (e.g., epoprostenol, treprostinil), or5. Treatment emergent worsening of pulmonary arterialhypertension |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
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 | 1 |