This is a clinical research study designed to evaluate an investigational new medication called sitaxsentan for the treatment of pulmonary arterial hypertension (patients with NYHA functional class II, III or IV). The purpose of this study is to evaluate the safety and effectiveness of two different doses of sitaxsentan, compared to placebo (inactive treatment) for the treatment of pulmonary arterial hypertension. Patients who complete this trial may be eligible to take part in an extension trial (Protocol FPH01-X). Eligible patients who receive placebo in the 12-week study cross over to receive sitaxsentan for the extension trial.

Inclusion Criteria:

1. NYHA Class II, III or IV
2. 16 to 75 years of age
3. Specific peak VO2 range
4. PPH, PAH due to connective tissue disease or select congenital heart disease
5. Qualifying cardiac catheterization
6. History of CXR and qualifying pulmonary function test
7. History of qualifying ventilation-perfusion lung scan
8. History of qualifying echocardiogram
9. Women of childbearing potential must use contraceptives
10. Stable dose of corticosteroids if prescribed

Exclusion Criteria:

1. Significant lung disease
2. Chronic liver disease
3. Uncontrolled sleep apnea
4. History of specific types of left heart disease
5. Any disorder that compromises ability to give informed consent
6. Uncontrolled sleep apnea
7. Inability to perform bicycle exercise test
8. On-going treatment with an experimental drug or device within the last 30 days
9. HIV infection
10. Specific liver dysfunction
11. Chronic renal disease
12. Pregnancy/Nursing
13. Chronic active hepatitis B or C
14. Chronic Flolan or Tracleer use within the last 30 days

• ICOS Corporation
• Texas Biotechnology Corporation