Pulmonary Arterial Hypertension MedDRA version: 20.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The full list of inclusion criteria is provided in Section 4.3 of the Protocol and all patients must fulfill all criteria. The main inclusion criteria are: 1. Signed informed consent prior to any study-mandated procedure 2. Symptomatic pulmonary arterial hypertension (PAH) 3. World Health Organization (WHO) Functional Class (FC) III 4. PAH etiology belonging to one of the following groups according to Nice classification: 1.1 Idiopathic PAH 1.2 Heritable PAH 1.3 Drug- and toxin-induced PAH 1.4.1 PAH associated with connective tissue disease 1.4.4 PAH associated with congenital heart diseases: only simple (atrial septal defect, ventricular septal defect, patent ductus arteriosus) congenital systemic to pulmonary shunts at least 2 year post surgical repair 5. Hemodynamic diagnosis of PAH confirmed by right heart catheterization (RHC) performed between Day -28 and Day 1 (inclusion RHC; RHC data obtained at study site within this time frame, prior to obtaining signed informed consent, are acceptable) showing: • mPAP = 25 mmHg and - PCWP or LVEDP = 12 mmHg and PVR = 4 Wood Units (WU) (320 dyn.sec.cm-5) or - 12 mmHg = PCWP or LVEDP = 15 mmHg and PVR = 6WU (480 dyn.sec.cm-5) - 6.6-minute walk distance (6MWD) = 150 m during screening 7. For patients treated with oral loop diuretics, treatment dose must be stable since at least 1 month prior to the inclusion RHC 8. For patients treated with PDE-5 inhibitors, treatment dose must be stable since at least 3 months prior to the inclusion RHC (initiation of PDE-5 inhibitors during screening is allowed after all screening assessments have been performed). 9. For patients treated with beta blockers, treatment dose must be stable since at least 1 month prior to the inclusion RHC 10. Men or women =18 and =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: The full list of exclusion criteria is provided in Section 4.4 of the Protocol and all patients must not fulfill any exclusion criterion. The main exclusion criteria are: 1. Body weight 35kg/m2. For patients with 30kg/m2 3 × ULN accompanied by an AST elevation > ULN at Screening. 19. Hemoglobin 3 times the upper limit of the normal range 21. Need for dialysis 22. Responders to acute vasoreactivity test based on medical history 23. Prior use of endothelin receptor antagonists, stimulators of soluble guanylate cyclase or prostacyclin or prostacyclin analogues 24. Treatment with strong inducers of CYP3A4 within 4 weeks prior to study treatment initiation (e.g., carbamazepine, rifampicin, rifabutin, phenytoin and St. John’s Wort) 25. Treatment with strong inhibitors of CYP3A4 within 4
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of macitentan on right ventricular and hemodynamic properties in patients with symptomatic PAH.; Secondary Objective: Secondary objective: To evaluate the safety and tolerability of macitentan in patients with symptomatic PAH Exploratory objectives: To investigate the effect of macitentan on disease-related circulating biomarkers in patients with symptomatic PAH To explore a potential association between change in right ventricular properties and clinical outcome in patients with symptomatic PAH To investigate the effect of macitentan on ventriculo-arterial coupling in patients with symptomatic PAH To evaluate the effect of macitentan on left ventricular properties in patients with symptomatic PAH ; Primary end point(s): Primary efficacy endpoint The study has two primary efficacy endpoints: -Change from baseline to Week 26 in Right Ventricular (RV) Stroke Volume (RVSV) assessed by cardiac MRI from pulmonary artery flow. -Ratio of Week 26 to baseline Pulmonary Vascular Resistance (PVR) assessed by RHC. ;Timepoint(s) of evaluation of this end point: Week 26 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints Change from baseline to Week 26 in: -RV End Diastolic Volume (RVEDV) -RV End Systolic Volume (RVESV) -RV Ejection Fraction (RVEF) -RV mass -six-minute walk distance (6MWD) -World Health Organization (WHO) Functional Class (FC) ;Timepoint(s) of evaluation of this end point: Week 26 | — |
Countries
Australia, France, Germany, Hong Kong, Israel, Italy, Malaysia, Netherlands, Russian Federation, Singapore, United Kingdom, United States
Contacts
Public ContactGlobal Medical Affairs
Actelion Pharmaceuticals Ltd.
Outcome results
None listed