Ensayos clínicos

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