Tezosentan in Pulmonary Arterial Hypertension

Inclusion Criteria:

1. Signed informed consent

2. Male and female patients 18 years of age or older

3. Patients with PAH according to one of the following subgroups of the Venice
Classification Group 1:

- Idiopathic (iPAH), or

- Familial/heritable (FPAH), or

- Associated (APAH) with collagen vascular disease

4. Modified NYHA functional class II-III

5. Documented hemodynamic diagnosis of PAH by right heart catheterization at Baseline:

- Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and

- Resting mean PVR ≥ 240 dyn•s•cm-5 and

- Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg

Exclusion Criteria:

1. Patients with PAH in Venice Classification Groups 2-5, and PAH Group 1 subgroups not
covered by inclusion criterion no. 3

2. Hypotensive patients (systemic systolic blood pressure < 100 mmHg)

3. Patients with body weight < 50 kg (110 lbs)

4. Patients with moderate or severe hepatic impairment (Child-Pugh B and C)

5. Patients with clinically significant chronic renal insufficiency (serum creatinine >
2.5mg/dL / 221µmol/L)

6. Patients who have received any endothelin receptor antagonist (ERA) and/or any
phosphodiesterase-5 (PDE-5) inhibitor within 28 days of Baseline

7. Patients who have received prostacyclin (epoprostenol) or prostacyclin analogs (e.g.,
treprostinil, iloprost) within 28 days of Baseline

8. Patients who have received any investigational drugs within 28 days of Baseline

9. Patients who have received cyclosporine A or tacrolimus within 28 days of Baseline

10. Psychotic, addictive or other disorder limiting the ability to provide informed
consent or to comply with the study

11. Life expectancy less than 12 months

12. Females who are lactating or pregnant or females who are not using a reliable method
of birth control (failure rate less than 1% per year) during the study and for at
least one month after study drug intake

13. Known hypersensitivity to any of the excipients of the drug formulation

14. Patients with positive response to vasoreactivity test