Efficacy and Safety of Upfront Combination of ΒΟsentan and ΤΑdalafil in Pulmonary Arterial Hypertension (BOTA-PAH)

Inclusion Criteria:

Male or females between 18 to 75 years of age at inclusion

Diagnosis of PAH due to the following:

• Idiopathic Primary Pulmonary Arterial Hypertension (IPAH)
• Hereditary PAH
• PAH secondary to connective tissue disease
• PAH diagnosis confirmed by right heart catheterization performed within 3 months prior to study enrolment Subjects must weigh at least 40 kg at inclusion Subject must have a current diagnosis of being in World Health Organisation (WHO) Functional Class II or III.

Treatment PAH naïve subjects PAH documented by

• mPAP ≥25mmHg,
• pulmonary capillary wedge pressure (PCWP) or
• left ventricular end-diastolic pressure (LVEDP) ≤15mmHg and
• PVR ≥3 Wood Units. Subject must walk a distance of ≥125m and ≤500m at the screening visit

Exclusion Criteria:

• History of pulmonary embolism
• No prior treatment with PDE-5 inhibitors
• History of chronic lung disease / restrictive lung disease (eg, chronic obstructive pulmonary disease (COPD) or scleroderma) with impairment of lung function
• Current treatment with nitrates or nitric oxide
• Significant (ie, >2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation
• History of cardiac arrest, respiratory arrest, hemodynamic collapse, CPR, ventricular tachycardia, ventricular fibrillation, or uncontrolled atrial fibrillation