A Dose Response Study of UT-15C SR in Patients With Exercise-Induced Pulmonary Hypertension

Inclusion Criteria-

A subject was eligible for inclusion in this study if all of the following criteria applied:

• Was between the ages of 18 and 75 years of age at Screening
• Weighed a minimum of 40 kilograms with a body mass index less than 40 kg/m2 at Screening
• Agreed to have right heart catheterization with exercise performed at Baseline and Week 12, or at the time of early discontinuation of study drug
• Had exercise-induced PH at Baseline (defined as a PAPm ≥ 30 mmHg during exercise).

Note: eligible subjects may or may not have had a PAPm ≥ 25 mmHg at rest

• Exercise-induced PH may have been:
• Idiopathic, heritable, drug- or toxin-induced PAH, or PAH associated with connective tissue diseases or HIV infection
• Due to ILD
• Due to sarcoidosis
• Had a Baseline pulmonary function tests as follows:
• Forced vital capacity (FVC) ≥ 50% (predicted)
• If FVC 15 mmHg or left ventricular ejection fraction (LVEF) < 45% (as assessed by either multigated acquisition [MUGA] scan, angiography or echocardiography), or symptomatic coronary artery disease (i.e., demonstrable ischemia either at rest or during exercise)
• Had acute pulmonary embolism (less than 6 months), chronic thromboembolic disease, pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis
• Had an atrial septostomy
• Had a current diagnosis of uncontrolled sleep disordered breathing
• Had PH associated with:
• chronic obstructive lung disease (COPD), cystic fibrosis, emphysema, alveolar hypoventilation disorders, chronic exposure to high altitude, developmental abnormalities, schistosomiasis, or chronic hemolytic anemia
• hematologic disorders (myeloproliferative disorders, splenectomy)
• metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders
• pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis
• tumoral obstruction, fibrosing mediastinitis, or extensive loss of lung tissue from surgery or trauma
• Had chronic renal insufficiency as defined by either a Screening creatinine value greater than 2.5 mg/dL (221 μmol/L) or the requirement for dialysis.
• Had liver function tests (AST or ALT) greater than three times the upper limit of normal at Screening.
• Had anemia as defined by a Screening hemoglobin value of less than 10 g/dL, active infection, or any other condition that would interfere with the interpretation of study assessments.
• Had uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
• Was pregnant or nursing.
• Had an unstable psychiatric condition or was mentally incapable of understanding the objectives, nature, or consequences of the trial, or had any condition which in the Investigator's opinion would constitute an unacceptable risk to the subject's safety.
• Was receiving an investigational drug, had an investigational device in place or had participated in an investigational drug or device study within 30 days prior to Screening.