A Study of Ubenimex in Patients With Pulmonary Arterial Hypertension (WHO Group 1)

Exclusion Criteria

• •Exclusions Related to Cardiovascular Disease
• •1. History of uncontrolled hypertension
• •2. Persistent hypotension at Screening.
• •3. Evidence or history of left-sided heart disease and/or clinically significant cardiac disease in which pulmonary hypertension is more likely WHO Group 2.
• •4. Acute decompensated heart failure within 1 month of Screening.
• •5. Recent initiation (\<8 weeks from Screening) or planned initiation of cardiopulmonary rehabilitation exercise program.
• •Exclusions Related to Pulmonary Disease
• •6. Newly diagnosed with PAH and not on PAH-specific therapy.
• •7. Pulmonary hypertension due to:
• •1. Uncorrected congenital systemic-to-pulmonary shunt.
• •2. Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis
• •3. Persistent pulmonary hypertension of the newborn
• •4. WHO clinical classification Groups 2-5
• •8. Evidence of significant airway and/or parenchymal lung disease.
• •9. Chronic infection related to tuberculosis or fungal or mycobacterial disease.
• •Exclusions Based on Other Medical Conditions
• •10. Chronic infections including, but not limited to tuberculosis (TB), hepatitis B virus (HBV) or hepatitis C virus (HCV).
• •11. History of portal hypertension or chronic liver disease, including positive serology for infection with HCV and/or HBV.
• •12. Evidence of active infection requiring intravenous or oral antibiotics within 4 weeks of Screening.
• •13. Body mass index ≥35.0 at Screening.
• •14. History of obstructive sleep apnea.
• •15. History of malignancy within the last 5 years, except nonmelanoma skin cancer and cervical carcinoma in situ treated with curative intent.
• •16. Neuropsychiatric disorders/symptoms or psychological conditions.
• •17. Pregnancy or breast-feeding
• •18. Prior treatment with B cell or lymphocyte-depleting agents (eg, rituximab, Campath)
• •Exclusions Based on Concomitant Medication Use
• •19. Concurrent regular use of another leukotriene pathway inhibitor, including over-the-counter medications or herbal remedies.
• •Exclusions Based on Laboratory Values
• •20. Significant/chronic renal insufficiency.
• •21. Transaminases (alanine transaminase, aspartate transaminase) levels \>3 × upper limit of normal (ULN) and/or bilirubin level \>2 × ULN.
• •22. Absolute neutrophil count \<1500 mm3.
• •23. Hemoglobin concentration \<9 g/dL at Screening.
• •24. Hepatic dysfunction as defined by Child-Pugh Class B or C