Safety of Sildenafil in Premature Infants

This will be a multi-center, randomized, placebo-controlled, sequential dose escalating,
double masked, safety data study of sildenafil in premature infants.

This is a Phase II study design, premature infants (inpatient in neonatal intensive care
units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) into 3
cohorts with escalating doses of sildenafil. There will be 40 randomized and dosed
participants in each cohort for a total of up to 120 participants. Cohort 1 sildenafil dose
will be 0.125 mg/kg q 8 hours IV or 0.25 mg/kg q 8 hours enteral. Cohort 2 sildenafil dose
will be 0.5 mg/kg q 8 hours IV or 1.0 mg/kg q 8 hours enteral. Cohort 3 sildenafil dose will
be 1 mg/kg q 8 hours IV or 2 mg/kg q 8 hours enteral.

Inclusion Criteria:

- Receiving positive airway pressure (nasal continuous airway pressure, nasal
intermittent positive pressure ventilation, or nasal cannula flow > 1LPM) or
mechanical ventilation (high frequency or conventional)

- <29 weeks gestational age at birth

- 7-28 (inclusive) days postnatal age at time of randomization

Exclusion Criteria:

- Currently receiving vasopressors

- Currently receiving inhaled nitric oxide

- Baseline mean arterial pressure < gestational age (in weeks) plus postnatal age (in
weeks) within 2 hours of sildenafil administration

- Known allergy to sildenafil

- Known sickle cell disease

- AST > 225 U/L < 72 hours prior to randomization

- ALT > 150 U/L < 72 hours prior to randomization