Safety of Sildenafil in Premature Infants

Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia

Describe the safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia and determine preliminary effectiveness and pharmacokinetics (PK) of sildenafil. Funding Source - FDA Office of Orphan Products Development (OOPD).

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
• Aspartate Aminotransferase (AST) > 225 U/L < 72 hours prior to randomization
• Alanine Aminotransferase (ALT) > 150 U/L < 72 hours prior to randomization