A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease

Exclusion Criteria

• •PAH associated with any other condition
• •Severe obstructive lung disease : FEV1∕ FVC \<0.5
• •Total lung capacity \<60% of normal predicted value
• •Unable or unwilling have a cardiac catheterization procedure
• •Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (6-MWT)
• •Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
• •Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
• •AST and ∕or ALT \> 3 times uln
• •Hemoglobin concentration \> 25% below the lower limit of normal
• •Systolic blood pressure \< 85 mm Hg
• •Pregnancy or breast-feeding
• •Treatment or planned treatment with another investigational drug
• •Treatment with an endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 2 months of inclusion
• •Treatment with calcineurin-inhibitors (i.e., cyclosporine A and tacrolimus), fluconazole, glibenclamide (glyburide) within 1 week of study start;
• •Known hypersensitivity to bosentan or any of the excipients