Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Males and females between 18 to 80 years of age inclusive at Screening
Weight ≥40 kg
Must have a diagnosis of WHO Group 1 PH
Have a World Health Organization (WHO) Classification of Functional Status Class II or III of patients with PH
Must meet hemodynamic criteria by means of a right heart catheterization
Meet pulmonary function test parameters
A 6 MWD test of ≥125m and ≤550m at the visit
Subjects must have a resting arterial oxygen saturation (SaO2) ≥90%, with or without supplemental oxygen, as measured by pulse oximetry at Screening
Subjects enrolled in a prescribed exercise program for pulmonary rehabilitation must be in a stable program for 3 months prior to Screening (Visit 1) and must agree to maintain their current level of rehabilitation throughout the study. If subjects are not enrolled in a prescribed exercise training program for pulmonary rehabilitation, they cannot enroll during the Screening/Baseline Period or throughout the study
If receiving simvastatin-containing products: dose should not exceed 20 mg/day
Subjects must be receiving no more than three of the following previously approved PAH therapies: phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor antagonist (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor agonists and must be on stable doses (≥3 months) at Screening (Visit 1)

Exclusion Criteria:

Contraindications for CMRI imaging
WHO Groups 2, 3, 4 and 5 Pulmonary Hypertension
Unrepaired congenital heart defects and significant congenital heart defects (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) repaired less than 1 year prior to Screening (Visit 1) (Group 1 classification of Pulmonary Hypertension)
QTcF > 500 msec
Acute myocardial infarction or acute coronary syndrome within the last 90 days
Cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days
Hospitalization for left heart failure within the last 90 days
Clinically significant aortic or mitral valve disease defined as greater than mild regurgitation or mild stenosis; pericardial constriction; restrictive or constrictive cardiomyopathy; left ventricular dysfunction (LVEF < 50%); left ventricular outflow obstruction; symptomatic coronary artery disease; autonomic hypotension; or fluid depletion
Chronic atrial fibrillation and life-threatening cardiac arrhythmias
Personal or family history of congenital prolonged QTc syndrome or sudden or sudden unexpected death due to a cardiac reason
Clinically significant anemia
Severe hepatic impairment or active chronic hepatitis
Receiving intravenous inotropes within 2 weeks prior to Screening
History of angina pectoris or other condition that was treated with long or short acting nitrates <12 weeks of Screening
Received prednisone doses >15mg/day or changes in immunosuppressive medications < 12 weeks prior to Screening (Visit 1)
Recent (within 1 year) history of abusing alcohol or illicit drugs.
History of any primary malignancy, with no evidence of disease for at least 5 years
Treatment with any investigational drug or device within 30 days or 5 half-lives