A Study of GMA301 in Subjects With Pulmonary Arterial Hypertension

Exclusion Criteria

• •Subjects who me et any of the following criteria will not be allowed to participate in this study:
• •1. Diagnosed with WHO Group II, III, IV, V of PH
• •2. Use of calcium channel blockers within 1 month prior to Screening
• •3. Systolic blood pressure (SBP) \>160 mmHg or diastolic blood pressure (DBP) \>100 mmHg at Screening
• •4. SBP \<90 mmHg at Screening
• •5. Pulmonary function test: FEV1 \<60% of predicted, TLC \<60% of predicted, DLCO \<60% of predicted
• •6. History of pulmonary embolism as judged by the Investigator
• •7. Uncontrolled sleep apnea at the discretion of the Investigator
• •8. Limited full participation in the 6MWT due to arthritic, neuromuscular, vascular or other diseases unrelated to PAH
• •9. History of acute cardiovascular and/or cerebrovascular events within 6 months before Screening
• •10. Echocardiogram (ECHO) demonstrating at least one of the following at Screening:
• •1. LVEF \<50%
• •2. Mean end-diastolic left ventricular septal and posterior wall thickness of \>12 mm
• •3. Left atrial (LA) area on apical 4 chamber view \>20 cm2
• •4. LA volume \>55 mL
• •5. LA volume index \>34 mL/m2
• •6. Significant valvular heart disease including moderate or severe mitral or aortic stenosis with an aortic valve area \<1.0 cm2 or mitral valve area \<1.5 cm2, greater than moderate aortic or mitral regurgitation, greater than moderate tricuspid or pulmonic stenosis
• •11. Restrictive, dilated or hypertrophic cardiomyopathy or constrictive pericarditis
• •12. Using non-oral prostacyclin when Screening
• •13. Laboratory parameters during Screening:
• •1. Baseline aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2 times the upper limit of normal (ULN) or total bilirubin ≥1.5 times ULN
• •2. Estimated glomerular filtration rate (eGFR) \<60 mL/min by Cockcroft-Gault formula
• •Online calculation available from https://www.kidney.org/professionals/KDOQI/gfr\_calculatorCoc
• •Cockcroft-Gault formula (1973):
• •Male: CCr=((l40-Age) × Weight)/(72×SCr)
• •Female: CCr={((l40-Age) × Weight)/(72×SCr)}× 0.85
• •CCr (creatinine clearance rate) = mL/min
• •Age = year
• •Weight = Kg
• •SCr (serum creatinine) = mg/dL
• •3. Hemoglobin concentration ≤100 g/L at Screening
• •14. QTc interval by Fridericia's criteria (QTcF) ≥500 msec at Screening
• •15. Malignancy within 5 years before Screening visit (with the exception of localized non-metastatic basal cell carcinoma of the skin, non-metastatic carcinoma of the prostate or in-situ carcinoma of the cervix excised with curative results)
• •16. Alcohol or drug abuse within 1 year before Screening
• •17. A psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study
• •18. History of organ transplantation
• •19. Pregnant or nursing females
• •20. History of HIV
• •21. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), or HIV antibody (HIV-ab)
• •22. Enrolled in another interventional study within 30 days before Screening
• •23. Any condition that, in the opinion of the Investigator, prevents a potential subject from safely participating in the study
• •24. Start a new exercise program or participate in any unusually strenuous physical exertion within 6 weeks prior to Screening.