Apabetalone for Pulmonary Arterial Hypertension

Inclusion Criteria

• •1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• •2. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• •3. Subject must be 18 to 75 years of age inclusive (18-80 years in case of PAH associated with scleroderma), at the time of signing the informed consent form.
• •4. PAH of idiopathic/hereditary/drug or toxin-induced origin; or associated with connective tissue diseases or simple congenital heart disease (atrial septal defect, ventricular septal defect, patent ductus arteriosus) corrected for \>1 year;
• •5. Mean PA pressure \>20mmHg, PVR \>400 dyn.s.cm-5 with PA wedge pressure ≤15mmHg) and absence of acute vasoreactivity;
• •6. WHO functional class II or III;
• •7. Clinically stable with unchanged vasoactive therapy for ≥3 months;
• •8. Two 6MWD of ≥ 150m (the latter being used as baseline value);
• •9. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined as Absence of known liver cirrhosis, Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days, Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Platelet count ≥ 100 x 109/L, Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 3.0 x institutional upper limit of normal and creatinine clearance estimated of ≥30 mL/min.
• •10. Patients must have a life expectancy ≥ 28 weeks.
• •11. Body mass index (BMI) within the range 18-40 kg/m2 (inclusive).
• •12. Patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study treatment;
• •13. Patients must be postmenopausal, free from menses for \>1 year, surgically sterilized, willing to use adequate contraception to prevent pregnancy, or agree to abstain from activities that could result in pregnancy; and agree to abstain lactating from enrollment through 3 months after the last dose of study treatment.
• •14. Male patients must use a condom during treatment and for 3 months after the last dose of apabetalone when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (see appendix B for acceptable methods) if they are of childbearing potential.
• •20. Participation in another clinical study with an investigational product administered in the last 3 months
• •21. Patients with a known hypersensitivity to apabetalone or any of the excipients of their formulations.
• •22. Inability to consent
• •23. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
• •24. Breast feeding women.