Remodulin as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn

Inclusion Criteria:

   - Parent(s) or legal guardian provided consent for the subject to participate

   - Weight at least 2 kg at Screening

   - Gestational age of ≥34 weeks and ≤14 days old at Screening

   - Diagnosis of PPHN, which was either idiopathic in nature or associated with the
   following: meconium aspiration syndrome, pneumonia, respiratory distress syndrome,
   sepsis, birth hypoxia, perinatal encephalopathy, or unilateral congenital
   diaphragmatic hernia

   - Currently requiring ventilator support

   - Two consecutive oxygenation index (OI) of 15 or greater separated by at least 30
   minutes, after receiving iNO for at least 3 hours

   - Echocardiographic (ECHO) evidence of pulmonary hypertension with elevated right
   ventricle pressure

   - Dedicated venous access for the administration of study drug (central line or
   peripherally inserted central venous catheter)

Exclusion Criteria:

   - Previous or concurrent use of a phosphodiesterase-5 inhibitor, endothelin receptor
   antagonist, or prostanoid

   - Significant congenital heart disease as detected by ECHO, minor valvular
   abnormalities, or expected transitional findings such as a patent foramen ovale, or
   patent ductus arteriosus.

   - Clinically significant, untreated active pneumothorax at Screening

   - Evidence of clinically significant bleeding at Screening

   - Necrotizing enterocolitis (≥Bells stage II at Screening)

   - Uncontrolled hypotension (mean systemic pressures ≤35 mmHg at Screening)

   - Uncontrolled coagulopathy and / or untreated thrombocytopenia (<50,000 platelets/µL at
   Screening)

   - History of severe (Grade 3 or 4) intracranial hemorrhage at Screening

   - Currently receiving extracorporeal mechanical oxygenation (ECMO) or had immediate
   plans to initiate ECMO

   - Expected duration on mechanical ventilation of <48 hours

   - Life expectancy was less than 2 months or had a lethal chromosomal anomaly

   - Contraindication to ECMO

   - Bilateral congenital diaphragmatic hernia

   - Active seizures at Screening

   - Currently participating in another clinical drug study