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

This study will enroll subjects with PPHN who do not show an adequate response to inhaled
nitric oxide with the hypothesis that the addition of intravenous (IV) Remodulin will reduce
the rate of clinical worsening as compared to standard of care. Additionally, this study aims
to evaluate the treatment effect of Remodulin and better understand the dosing and
pharmacokinetics in the neonatal population.

Inclusion Criteria:

- Parent(s) or guardian provides consent for the subject to participate, as per
institutional policy

- At least 2 kg at Screening

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

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

- Currently requiring ventilator support

- Receiving iNO with two OIs of 15 or greater separated by at least 30 minutes after
receiving iNO for at least 3 hours

- Echocardiographic 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 (PDE5i), endothelin
receptor antagonist (ERA), or prostanoid

- Significant congenital heart disease (CHD) as detected by ECHO (excluding presence of
minor defects such as small secundum atrial septal defect (ASD), minor valvular
abnormalities, or expected transitional findings such as a patent foramen ovale (PFO),
or patent ductus arteriosus (PDA). Subjects with small muscular, restrictive
ventricular septal defect (VSD) may be enrolled

- Clinically significant, untreated active pneumothorax at Screening

- Evidence of clinically significant bleeding

- Necrotizing entercolitis; ≥ Bells stage II at Screening

- Uncontrolled hypotension; mean systemic pressures ≤ 35 mmHg at Screening.

- Uncontrolled coagulopathy and / or untreated thrombocytopenia; defined as <50,000
platelets /µL at Screening

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

- Currently receiving ECMO or has immediate plans to initiate ECMO

- Expected duration on mechanical ventilation of less than 48 hours

- Life expectancy is less than two months or has a lethal chromosomal anomaly

- Contraindication to ECMO

- Bilateral congenital diaphragmatic hernia

- Active seizures at Screening

- Currently participating in another clinical drug study (excluding observational
registries)