To assess the effects of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension MedDRA version: 9.1 Level: LLT Classification code 10064911 Term: Pulmonary arterial hypertension
Conditions
Interventions
Product Name: ACT-064992
Product Code: ACT-064992
Pharmaceutical Form: Tablet
CAS Number: 441798-33-0
Current Sponsor code: ACT-064992
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed informed consent prior to initiation of any study mandated procedure. 2.Patients with symptomatic pulmonary arterial hypertension (PAH) in modified WHO functional class II to IV. 3.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; or iv.Drugs and toxins. 4.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 left ventricular end diastolic pressure (LVEDP) = 320 dyn*sec/cm5. ?For patients who participate in the pharmacokinetic/ pharmacodynamic substudy, hemodynamic evaluation must have been performed within 3 months prior to randomization. ?For all other patients, hemodynamic evaluation must have been performed within 1 year prior to randomization. 5.6-minute walk distance (6MWD) >= 50 m at screening and randomization The 6MWT performed at screening and randomization must satisfy the following requirements: • 6MWT distance must be > 50 m or patient cannot be included in the study. • 6MWT #2 (at Randomization) distance should be within 10% of 6MWT #1 distance (at Screening) or a third test is required (6MWT #3). • 6MWT #3 (at Randomization) distance should be within 10% of 6MWT #2 distance or the patient cannot be included in the study. 6.Men or women >= 12 years of age (women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception, men with a female partner of child-bearing potential should use a condom). Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher’s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy. 2.PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected. 3.PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis. 4.Persistent pulmonary hypertension of the newborn. 5.Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification. 6.Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) 1.5 times the upper limit of normal. 11.Hemoglobin < 75% of the lower limit of the normal range. 12.Systolic blood pressure < 100 mmHg. 13.Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements. 14.Pregnant or breast-feeding. 15.Known concomitant life-threatening disease with a life expectancy < 12 months. 16.Body weight < 40 kg. 17.Any condition that prevents compliance with the protocol or adherence to therapy. 18.Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise. 19.Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization. 20.Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mTOR inhibitors). 21. Treatment with CYP3A inducers within 4 weeks prior to randomization. 22.Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients. 23.Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To demonstrate that either dose of ACT-064992 prolongs the time to the first morbidity or mortality event in patients with symptomatic pulmonary arterial hypertension. ; Secondary Objective: •To demonstrate that either dose of ACT-064992 improves exercise capacity and WHO functional class, and prolongs the time to death or hospitalization for PAH in patients with symptomatic pulmonary arterial hypertension. •To evaluate the safety and tolerability of ACT-064992 in patients with symptomatic pulmonary arterial hypertension. ; Primary end point(s): Primary endpoint Time from start of treatment to first morbidity or mortality event, defined as follows: 1.Death, or 2.Atrial septostomy, or 3.Lung transplantation, or 4.Initiation of intravenous or subcutaneous prostanoids (e.g., epoprostenol, treprostinil), or 5.Other worsening of pulmonary arterial hypertension. Other worsening of pulmonary arterial hypertension is defined by the combination of all of the three following components: •A decrease in 6MWD of at least 15% from baseline that should be confirmed by two 6-minute walk tests, performed on different days, within 2 weeks AND •Worsening of PAH symptoms (1) AND •Need for new treatment(s) for PAH (2) (1) Worsening of PAH symptoms must include at least one of the following: ?WHO functional class increased, or no change in patients in WHO class IV at baseline ?Appearance or worsening of signs/symptoms of right heart failure that did not respond to oral diuretic therapy (2) New treatments for PAH are: ?oral or inhaled prostanoids (e.g., iloprost) ?oral phosphodiesterase inhibitors (e.g., sildenafil) | — |
Countries
Austria, Belgium, Bulgaria, Denmark, Finland, France, Germany, Italy, Netherlands, Portugal, Slovakia, Sweden, United Kingdom
Outcome results
None listed