Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA

This study is to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in up to four escalating doses to preterm neonates 26 to 28 weeks gestational age who are receiving nCPAP for RDS compared to neonates receiving nCPAP alone.

This study was a multicenter, randomized, controlled, open-label, dose-escalation study, conducted to evaluate the safety and tolerability of lucinactant for inhalation in conjunction with nasal continuous positive airway pressure (nCPAP) in comparison with nCPAP alone. The study was to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in 4 escalating doses.

For this study, lucinactant for inhalation refers to the active investigational agent, lyophilized lucinactant, in combination with the prototype investigational delivery device. Reconstituted lyophilized lucinactant was aerosolized by the investigational device and introduced into the nCPAP circuit. Those randomized to the control arm continued to receive nCPAP alone. Dose assignments were unblinded, as the primary objective of this study was safety and tolerability.

Preterm neonates with respiratory distress syndrome (RDS) between 26 and 28 completed weeks PMA who were within the first 20 hours after birth and who had successful implementation of controlled nCPAP within 90 minutes of birth were considered to be potential subjects. Before study enrollment, legal guardians were provided a written informed consent form (ICF) for each potential subject.

Eligibility Criteria:
Inclusion Criteria:

1. Informed consent from a legally authorized representative.
2. Gestational age 26 to 28 completed weeks post menstrual age (PMA).
3. Successful implementation of controlled nCPAP within 90 minutes after birth.
4. Spontaneous breathing.
5. Chest radiograph consistent with RDS.
6. Within the first 20 hours after birth, have an nCPAP of 5 to 6 cm H2O to maintain oxygen saturation measured by pulse oximetry (SpO2) of 88% to 95% with a fraction of inspired oxygen (FiO2) of 0.25 to 0.50 that is clinically indicated for at least 30 minutes. Transient (\<10 minutes) FiO2 excursions below 0.25 or above 0.50 did not reset the 30 minute requirement.

Exclusion Criteria:

1. Heart rate that cannot be stabilized above 100 beats/minute within 5 minutes of birth.
2. Recurrent episodes of apnea occurring after the initial newborn resuscitation period (ie, 10 minutes after birth) requiring intermittent positive pressure breaths using inflating pressures above the set CPAP pressure administered manually or mechanically through any patient interface.
3. A 5 minute Apgar score \< 5.
4. Major congenital malformation(s) and cranial/facial abnormalities that preclude nCPAP, diagnosed antenatally or immediately after birth.
5. Other diseases or conditions potentially interfering with cardiopulmonary function (eg, hydrops fetalis or congenital infection such as TORCH).
6. Known or suspected chromosomal abnormality or syndrome.
7. Premature rupture of membranes (PROM) \> 2 weeks.
8. Evidence of hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis.
9. Need for endotracheal intubation and mechanical ventilation.
10. Has been administered: another investigational agent or investigational medical device, any other surfactant agent, steroid treatment after birth.