Pulmonary arterial hypertension MedDRA version: 18.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
ACTELION Pharmaceuticals France
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to any study-mandated procedure. 2. Male or female = 18 and = 75 years of age at screening. 3. Initial PAH diagnosis =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Any PAH-specific drug therapy [e. g. any endothelin receptor antagonist, phosphodiesterase-5 inhibitors (PDE-5i), soluble guanylate cyclase stimulator, prostacyclin, prostacyclin analog, or prostacyclin receptor agonist] at any time prior to Day 1 (single-dose administration for vasoreactivity testing is permitted; previous iloprost used intermittently for the treatment of digital ulcers or Raynaud’s phenomenon is permitted if stopped > 6 months prior to Day 1). 2. Subjects who changed the dose or discontinued calcium channel blockers within 3 months prior to Day 1. 3. Initiation of diuretics within 1 week prior to RHC. 4. Subjects on oral diuretics in whom the dose has not been stable for at least 1 week prior to RHC. 5. Treatment with other PDE-5i for erectile dysfunction. 6. Treatment with strong inducers of CYP3A4 (e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John’s wort) = 28 days prior to Day 1. 7. Treatment with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, boceprevir, telaprevir, saquinavir, lopinavir, fosamprenavir, darunavir, tipranavir, atazanavir, nelfinavir, amprenavir, indinavir) = 28 days prior to Day 1. 8. History of priapism. 9. Significant aortic and mitral valve disease. 10. Pericardial constriction. 11. Significant left ventricular dysfunction in the opinion of the investigator. 12. Life-threatening arrhythmia. 13. Uncontrolled hypertension. 14. Symptomatic coronary artery disease. 15. Cardio-pulmonary rehabilitation program based on exercise (planned, or started = 12 weeks prior to Day 1). 16. Body mass index (BMI) > 40 kg/m2 at screening. 17. Acute myocardial infarction = 12 weeks prior to Day 1. 18. Known permanent atrial fibrillation. 19. Low blood pressure 3 x ULN accompanied by AST > ULN (assessed by central laboratory at screening); and/or Child Pugh Class C. 26. Serum AST and/or ALT > 3 x ULN (assessed by central laboratory at screening). 27. Porto-pulmonary hypertension. 28. Hemoglobin < 100 g/L assessed by central laboratory at screening. 29. Hypersensitivity to any active substance or excipient of macitentan or tad
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To document the effect of first line dual oral combination therapy with macitentan 10mg and tadalafil 40mg on pulmonary vascular resistance (PVR) in treatment-naïve patients with newly diagnosed pulmonary arterial hypertension (PAH).;Secondary Objective: To document the effect of a first line dual oral combination therapy with macitentan 10mg and tadalafil 40mg on cardio-pulmonary hemodynamic parameters other than PVR, on exercise capacity and disease severity, on NT-proBNP and on safety and tolerability in treatment-naïve patients with newly diagnosed PAH.;Primary end point(s): The primary endpoint is the ratio of Week 16 to baseline PVR.;Timepoint(s) of evaluation of this end point: Baseline and Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percentage of patients with clinically meaningful improvement of PVR (decrease = 30% from baseline to Week 16). • Change from baseline to Week 16 in mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), cardiac index (CI), total pulmonary resistance (TPR), and mixed venous oxygen saturation (SvO2), all measured at rest. • Change from baseline to Week 16 in 6-minute walk distance (6MWD). • Change from baseline to Week 16 in WHO functional class. • Percentage of patients with improvement/worsening of WHO functional class from baseline to Week 16. • Change in NT-proBNP from Baseline to Week 16. ;Timepoint(s) of evaluation of this end point: Baseline and Week 16 | — |
Countries
France
Contacts
Public ContactVirginie Gressin
ACTELION Pharmaceuticals France
Outcome results
None listed