Respiratory Distress Syndrome
Conditions
Brief summary
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.
Detailed description
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.
Interventions
COMBINATION_PRODUCTLucinactant for inhalation
Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product)
DEVICEnCPAP alone
nCPAP therapy
Sponsors
Windtree Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
26 Weeks to 28 Weeks
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Air Leak | 7 days | Number of participants with air leak (includes pneumothorax, pulmonary interstitial emphysema (PIE), pneumomediastinum, pneumopericardium, subcutaneous emphysema) |
| Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Randomization to 24 Hours Post Randomization | Number of Participants with adverse events that were experienced during the initial study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bronchopulmonary Dysplasia | Randomization to 36 weeks PMA | Number of participants with bronchopulmonary dysplasia (BPD) and number of participants alive and without BPD at 36 weeks post-menstrual age (PMA) |
| Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure | Randomization to 72 Hours Post Randomization | Participants who required intubation for mechanical ventilation or surfactant administration were defined as having failed nCPAP |
| FiO2 | Randomization to 72 hours post randomization | Observed and change from baseline measurements for fraction of inspired oxygen (FiO2). Values represent the amount (fraction) of oxygen in the air the participant inspires; the values themselves do not have units. The normal amount of oxygen in air (room air) is 21%, or 0.21. |
| Number of Participants With Complications of Prematurity | Randomization to 36 weeks PMA | Number of participants with pre-specified common complications of prematurity. |
| Death | Randomization to 36 weeks PMA | Number of participants who died during the study |
| Number of Participants With Worsening of Respiratory Status Criteria | Randomization to 72 Hours Post Randomization | Number of participants with worsening in one of 12 respiratory status criteria through 72 hours post randomization (need for additional surfactant therapy, desaturation \< 80%, heart rate \< 100 bpm, sustained fraction of inspired oxygen (FiO2) \> 0.50, arterial carbon dioxide (PCO2) \> 65 mmHg, sustained apnea, persistent arterial pH \< 7.2, intubation for any reason, nCPAP \> 7 cmH2O, initiation of intermittent positive pressure ventilation, death, principal investigator determination of worsening status) |
Other
| Measure | Time frame | Description |
|---|---|---|
| nCPAP Failure Without Treatment Interruptions | Randomization to 72 Hours Post Randomization | Number of subjects requiring mechanical ventilation or surfactant administration (nCPAP failure) but did not have a treatment interruption |
Countries
Canada, Chile, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 mg/kg Lucinactant for inhalation 50 mg TPL/kg with nCPAP
1 repeat dose allowed if repeat dosing criteria are met.
Lucinactant for inhalation: Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product) | 8 |
| 75 mg/kg Lucinactant for inhalation 75 mg TPL/kg with nCPAP
1 repeat dose allowed if repeat dosing criteria are met.
Lucinactant for inhalation: Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product) | 8 |
| 100 mg/kg Lucinactant for inhalation 100 mg TPL/kg with nCPAP
1 repeat dose allowed if repeat dosing criteria are met.
Lucinactant for inhalation: Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product) | 8 |
| 150 mg/kg Lucinactant for inhalation 150 mg TPL/kg with nCPAP
1 repeat dose will be allowed if repeat dosing criteria are met.
Lucinactant for inhalation: Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product) | 0 |
| nCPAP Alone nCPAP therapy alone
nCPAP alone: nCPAP therapy | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | 50 mg/kg | 75 mg/kg | 100 mg/kg | 150 mg/kg | nCPAP Alone | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 8 Participants | 8 Participants | 0 Participants | 24 Participants | 48 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Gestational Age | 27.6 weeks STANDARD_DEVIATION 0.61 | 27.2 weeks STANDARD_DEVIATION 1.06 | 27.2 weeks STANDARD_DEVIATION 0.84 | — | 27.5 weeks STANDARD_DEVIATION 0.76 | 27.4 weeks STANDARD_DEVIATION 0.84 |
| Apgar Score at Five Minutes | 7.8 Scores on a scale | 6.4 Scores on a scale | 8.1 Scores on a scale | — | 7.9 Scores on a scale | 7.7 Scores on a scale |
| Apgar Score at One Minute | 5.4 Scores on a scale | 5.5 Scores on a scale | 6.4 Scores on a scale | — | 5.8 Scores on a scale | 5.8 Scores on a scale |
| Birth Weight | 1052 g STANDARD_DEVIATION 174.7 | 855 g STANDARD_DEVIATION 84.6 | 839 g STANDARD_DEVIATION 224.9 | — | 1005 g STANDARD_DEVIATION 238.8 | 960 g STANDARD_DEVIATION 209.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | — | 7 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 6 Participants | — | 17 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | — | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | — | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 1 Participants | — | 2 Participants | 7 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 4 Participants | — | 20 Participants | 32 Participants |
| Region of Enrollment Canada | 1 participants | 3 participants | 4 participants | — | 8 participants | 16 participants |
| Region of Enrollment Chile | 0 participants | 0 participants | 0 participants | — | 1 participants | 1 participants |
| Region of Enrollment Poland | 0 participants | 2 participants | 0 participants | — | 3 participants | 5 participants |
| Region of Enrollment United States | 7 participants | 3 participants | 4 participants | — | 12 participants | 26 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 5 Participants | — | 8 Participants | 21 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 3 Participants | — | 16 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 8 | 1 / 8 | 0 / 8 | 0 / 0 | 0 / 24 |
| other Total, other adverse events | 8 / 8 | 8 / 8 | 8 / 8 | 0 / 0 | 24 / 24 |
| serious Total, serious adverse events | 4 / 8 | 3 / 8 | 2 / 8 | 0 / 0 | 6 / 24 |
Outcome results
Primary
Number of Participants With Air Leak
Number of participants with air leak (includes pneumothorax, pulmonary interstitial emphysema (PIE), pneumomediastinum, pneumopericardium, subcutaneous emphysema)
Time frame: 7 days
Population: This dose-escalation study was terminated after completion of the 100 mg/kg group for administrative purposes. No participants were enrolled in the 150 mg/kg group or received 150 mg/kg.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg/kg | Number of Participants With Air Leak | 3 Participants |
| 75 mg/kg | Number of Participants With Air Leak | 0 Participants |
| 100 mg/kg | Number of Participants With Air Leak | 2 Participants |
| nCPAP Alone | Number of Participants With Air Leak | 4 Participants |
Primary
Number of Participants With Peri-Dosing Adverse Events - Initial Dose
Number of Participants with adverse events that were experienced during the initial study treatment
Time frame: Randomization to 24 Hours Post Randomization
Population: Safety Population. Peri-dosing events are events that occur during study treatment. Since this was an open-label study, no peri-dosing events were recorded for nCPAP alone. Any adverse events that occurred during the corresponding time for nCPAP alone were recorded as adverse events but not peri-dosing events.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 50 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Apnea | 1 Participants |
| 50 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Gagging/regurgitation | 0 Participants |
| 50 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Bradycardia | 0 Participants |
| 50 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Desaturation | 1 Participants |
| 50 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Pallor | 0 Participants |
| 75 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Gagging/regurgitation | 0 Participants |
| 75 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Bradycardia | 2 Participants |
| 75 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Desaturation | 2 Participants |
| 75 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Apnea | 1 Participants |
| 75 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Pallor | 0 Participants |
| 100 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Pallor | 0 Participants |
| 100 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Apnea | 1 Participants |
| 100 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Bradycardia | 1 Participants |
| 100 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Gagging/regurgitation | 0 Participants |
| 100 mg/kg | Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Desaturation | 3 Participants |
Secondary
Bronchopulmonary Dysplasia
Number of participants with bronchopulmonary dysplasia (BPD) and number of participants alive and without BPD at 36 weeks post-menstrual age (PMA)
Time frame: Randomization to 36 weeks PMA
Population: Intent-to-Treat Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 50 mg/kg | Bronchopulmonary Dysplasia | BPD | 0 Participants |
| 50 mg/kg | Bronchopulmonary Dysplasia | Alive and Without BPD | 7 Participants |
| 75 mg/kg | Bronchopulmonary Dysplasia | Alive and Without BPD | 7 Participants |
| 75 mg/kg | Bronchopulmonary Dysplasia | BPD | 0 Participants |
| 100 mg/kg | Bronchopulmonary Dysplasia | BPD | 0 Participants |
| 100 mg/kg | Bronchopulmonary Dysplasia | Alive and Without BPD | 8 Participants |
| nCPAP Alone | Bronchopulmonary Dysplasia | BPD | 6 Participants |
| nCPAP Alone | Bronchopulmonary Dysplasia | Alive and Without BPD | 18 Participants |
Secondary
Death
Number of participants who died during the study
Time frame: Randomization to 36 weeks PMA
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg/kg | Death | 1 Participants |
| 75 mg/kg | Death | 1 Participants |
| 100 mg/kg | Death | 0 Participants |
| 150 mg/kg | Death | 0 Participants |
| nCPAP Alone | Death | 0 Participants |
Secondary
FiO2
Observed and change from baseline measurements for fraction of inspired oxygen (FiO2). Values represent the amount (fraction) of oxygen in the air the participant inspires; the values themselves do not have units. The normal amount of oxygen in air (room air) is 21%, or 0.21.
Time frame: Randomization to 72 hours post randomization
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 50 mg/kg | FiO2 | Baseline (Randomization) | 0.31 Fraction of oxygen in inspired air | Standard Deviation 0.058 |
| 50 mg/kg | FiO2 | 60 Minutes Post Randomization - Observed | 0.31 Fraction of oxygen in inspired air | Standard Deviation 0.064 |
| 50 mg/kg | FiO2 | 60 Minutes Post Randomizati - Change from Baseline | 0.01 Fraction of oxygen in inspired air | Standard Deviation 0.01 |
| 50 mg/kg | FiO2 | 3 Hours Post Randomization - Observed | 0.37 Fraction of oxygen in inspired air | Standard Deviation 0.191 |
| 50 mg/kg | FiO2 | 3 Hours Post Randomizaiton - Change from Baseline | 0.06 Fraction of oxygen in inspired air | Standard Deviation 0.154 |
| 50 mg/kg | FiO2 | 12 Hours Post Randomization - Observed | 0.30 Fraction of oxygen in inspired air | Standard Deviation 0.114 |
| 50 mg/kg | FiO2 | 12 Hours Post Randomization - Change from Baseline | -0.02 Fraction of oxygen in inspired air | Standard Deviation 0.137 |
| 50 mg/kg | FiO2 | 24 Hours Post Randomized - Observed | 0.28 Fraction of oxygen in inspired air | Standard Deviation 0.093 |
| 50 mg/kg | FiO2 | 24 Hours Post Randomized - Change from Baseline | -0.03 Fraction of oxygen in inspired air | Standard Deviation 0.072 |
| 50 mg/kg | FiO2 | 48 Hours Post Randomized - Observed | 0.28 Fraction of oxygen in inspired air | Standard Deviation 0.058 |
| 50 mg/kg | FiO2 | 48 Hours Post Randomized - Change from Baseline | -0.03 Fraction of oxygen in inspired air | Standard Deviation 0.083 |
| 50 mg/kg | FiO2 | 72 Hours Post Randomized - Observed | 0.30 Fraction of oxygen in inspired air | Standard Deviation 0.105 |
| 50 mg/kg | FiO2 | 72 Hours Post Randomized - Change from Baseline | -0.02 Fraction of oxygen in inspired air | Standard Deviation 0.133 |
| 75 mg/kg | FiO2 | 3 Hours Post Randomization - Observed | 0.37 Fraction of oxygen in inspired air | Standard Deviation 0.12 |
| 75 mg/kg | FiO2 | 72 Hours Post Randomized - Change from Baseline | -0.10 Fraction of oxygen in inspired air | Standard Deviation 0.071 |
| 75 mg/kg | FiO2 | 48 Hours Post Randomized - Change from Baseline | -0.09 Fraction of oxygen in inspired air | Standard Deviation 0.075 |
| 75 mg/kg | FiO2 | 24 Hours Post Randomized - Observed | 0.25 Fraction of oxygen in inspired air | Standard Deviation 0.044 |
| 75 mg/kg | FiO2 | 60 Minutes Post Randomizati - Change from Baseline | 0.02 Fraction of oxygen in inspired air | Standard Deviation 0.024 |
| 75 mg/kg | FiO2 | Baseline (Randomization) | 0.33 Fraction of oxygen in inspired air | Standard Deviation 0.071 |
| 75 mg/kg | FiO2 | 48 Hours Post Randomized - Observed | 0.24 Fraction of oxygen in inspired air | Standard Deviation 0.038 |
| 75 mg/kg | FiO2 | 24 Hours Post Randomized - Change from Baseline | -0.09 Fraction of oxygen in inspired air | Standard Deviation 0.046 |
| 75 mg/kg | FiO2 | 12 Hours Post Randomization - Observed | 0.30 Fraction of oxygen in inspired air | Standard Deviation 0.117 |
| 75 mg/kg | FiO2 | 3 Hours Post Randomizaiton - Change from Baseline | 0.00 Fraction of oxygen in inspired air | Standard Deviation 0.066 |
| 75 mg/kg | FiO2 | 60 Minutes Post Randomization - Observed | 0.35 Fraction of oxygen in inspired air | Standard Deviation 0.063 |
| 75 mg/kg | FiO2 | 72 Hours Post Randomized - Observed | 0.23 Fraction of oxygen in inspired air | Standard Deviation 0.023 |
| 75 mg/kg | FiO2 | 12 Hours Post Randomization - Change from Baseline | -0.07 Fraction of oxygen in inspired air | Standard Deviation 0.074 |
| 100 mg/kg | FiO2 | 48 Hours Post Randomized - Change from Baseline | -0.09 Fraction of oxygen in inspired air | Standard Deviation 0.091 |
| 100 mg/kg | FiO2 | 3 Hours Post Randomization - Observed | 0.37 Fraction of oxygen in inspired air | Standard Deviation 0.107 |
| 100 mg/kg | FiO2 | 3 Hours Post Randomizaiton - Change from Baseline | 0.00 Fraction of oxygen in inspired air | Standard Deviation 0.047 |
| 100 mg/kg | FiO2 | 72 Hours Post Randomized - Change from Baseline | -0.12 Fraction of oxygen in inspired air | Standard Deviation 0.066 |
| 100 mg/kg | FiO2 | 12 Hours Post Randomization - Observed | 0.30 Fraction of oxygen in inspired air | Standard Deviation 0.068 |
| 100 mg/kg | FiO2 | 12 Hours Post Randomization - Change from Baseline | -0.08 Fraction of oxygen in inspired air | Standard Deviation 0.09 |
| 100 mg/kg | FiO2 | 72 Hours Post Randomized - Observed | 0.25 Fraction of oxygen in inspired air | Standard Deviation 0.05 |
| 100 mg/kg | FiO2 | 24 Hours Post Randomized - Observed | 0.28 Fraction of oxygen in inspired air | Standard Deviation 0.077 |
| 100 mg/kg | FiO2 | 24 Hours Post Randomized - Change from Baseline | -0.08 Fraction of oxygen in inspired air | Standard Deviation 0.105 |
| 100 mg/kg | FiO2 | 48 Hours Post Randomized - Observed | 0.29 Fraction of oxygen in inspired air | Standard Deviation 0.071 |
| 100 mg/kg | FiO2 | Baseline (Randomization) | 0.37 Fraction of oxygen in inspired air | Standard Deviation 0.072 |
| 100 mg/kg | FiO2 | 60 Minutes Post Randomization - Observed | 0.37 Fraction of oxygen in inspired air | Standard Deviation 0.09 |
| 100 mg/kg | FiO2 | 60 Minutes Post Randomizati - Change from Baseline | 0.01 Fraction of oxygen in inspired air | Standard Deviation 0.044 |
| nCPAP Alone | FiO2 | 48 Hours Post Randomized - Observed | 0.31 Fraction of oxygen in inspired air | Standard Deviation 0.188 |
| nCPAP Alone | FiO2 | 24 Hours Post Randomized - Observed | 0.29 Fraction of oxygen in inspired air | Standard Deviation 0.143 |
| nCPAP Alone | FiO2 | 3 Hours Post Randomization - Observed | 0.29 Fraction of oxygen in inspired air | Standard Deviation 0.082 |
| nCPAP Alone | FiO2 | Baseline (Randomization) | 0.32 Fraction of oxygen in inspired air | Standard Deviation 0.061 |
| nCPAP Alone | FiO2 | 12 Hours Post Randomization - Change from Baseline | 0.00 Fraction of oxygen in inspired air | Standard Deviation 0.172 |
| nCPAP Alone | FiO2 | 12 Hours Post Randomization - Observed | 0.33 Fraction of oxygen in inspired air | Standard Deviation 0.181 |
| nCPAP Alone | FiO2 | 60 Minutes Post Randomizati - Change from Baseline | 0.01 Fraction of oxygen in inspired air | Standard Deviation 0.162 |
| nCPAP Alone | FiO2 | 60 Minutes Post Randomization - Observed | 0.34 Fraction of oxygen in inspired air | Standard Deviation 0.159 |
| nCPAP Alone | FiO2 | 3 Hours Post Randomizaiton - Change from Baseline | -0.03 Fraction of oxygen in inspired air | Standard Deviation 0.082 |
| nCPAP Alone | FiO2 | 24 Hours Post Randomized - Change from Baseline | -0.04 Fraction of oxygen in inspired air | Standard Deviation 0.14 |
| nCPAP Alone | FiO2 | 72 Hours Post Randomized - Change from Baseline | -0.05 Fraction of oxygen in inspired air | Standard Deviation 0.133 |
| nCPAP Alone | FiO2 | 72 Hours Post Randomized - Observed | 0.27 Fraction of oxygen in inspired air | Standard Deviation 0.119 |
| nCPAP Alone | FiO2 | 48 Hours Post Randomized - Change from Baseline | -0.02 Fraction of oxygen in inspired air | Standard Deviation 0.191 |
Secondary
Number of Participants With Complications of Prematurity
Number of participants with pre-specified common complications of prematurity.
Time frame: Randomization to 36 weeks PMA
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 50 mg/kg | Number of Participants With Complications of Prematurity | Intraventicular Hemorrhage | 0 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Pulmonary Hemorrhage | 1 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Retinopathy of Prematurity | 2 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Cystic Periventricular Leukomalcia | 0 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Apnea | 8 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Acquired Sepsis | 2 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Necrotizing Enterocolitis | 1 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Patent Ductus Arteriosus | 3 Participants |
| 50 mg/kg | Number of Participants With Complications of Prematurity | Subjects with Any Complication | 8 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Patent Ductus Arteriosus | 3 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Intraventicular Hemorrhage | 1 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Pulmonary Hemorrhage | 0 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Acquired Sepsis | 2 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Subjects with Any Complication | 7 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Apnea | 5 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Retinopathy of Prematurity | 1 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Necrotizing Enterocolitis | 1 Participants |
| 75 mg/kg | Number of Participants With Complications of Prematurity | Cystic Periventricular Leukomalcia | 0 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Patent Ductus Arteriosus | 4 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Subjects with Any Complication | 7 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Acquired Sepsis | 2 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Apnea | 6 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Cystic Periventricular Leukomalcia | 0 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Pulmonary Hemorrhage | 1 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Intraventicular Hemorrhage | 3 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Necrotizing Enterocolitis | 1 Participants |
| 100 mg/kg | Number of Participants With Complications of Prematurity | Retinopathy of Prematurity | 1 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Intraventicular Hemorrhage | 4 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Cystic Periventricular Leukomalcia | 1 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Apnea | 19 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Retinopathy of Prematurity | 9 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Necrotizing Enterocolitis | 1 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Acquired Sepsis | 5 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Pulmonary Hemorrhage | 1 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Patent Ductus Arteriosus | 10 Participants |
| nCPAP Alone | Number of Participants With Complications of Prematurity | Subjects with Any Complication | 22 Participants |
Secondary
Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure
Participants who required intubation for mechanical ventilation or surfactant administration were defined as having failed nCPAP
Time frame: Randomization to 72 Hours Post Randomization
Population: Intent-to-Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg/kg | Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure | 5 Participants |
| 75 mg/kg | Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure | 7 Participants |
| 100 mg/kg | Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure | 5 Participants |
| nCPAP Alone | Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure | 16 Participants |
Secondary
Number of Participants With Worsening of Respiratory Status Criteria
Number of participants with worsening in one of 12 respiratory status criteria through 72 hours post randomization (need for additional surfactant therapy, desaturation \< 80%, heart rate \< 100 bpm, sustained fraction of inspired oxygen (FiO2) \> 0.50, arterial carbon dioxide (PCO2) \> 65 mmHg, sustained apnea, persistent arterial pH \< 7.2, intubation for any reason, nCPAP \> 7 cmH2O, initiation of intermittent positive pressure ventilation, death, principal investigator determination of worsening status)
Time frame: Randomization to 72 Hours Post Randomization
Population: Intent-to-Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg/kg | Number of Participants With Worsening of Respiratory Status Criteria | 6 Participants |
| 75 mg/kg | Number of Participants With Worsening of Respiratory Status Criteria | 7 Participants |
| 100 mg/kg | Number of Participants With Worsening of Respiratory Status Criteria | 6 Participants |
| nCPAP Alone | Number of Participants With Worsening of Respiratory Status Criteria | 18 Participants |
Other Pre-specified
nCPAP Failure Without Treatment Interruptions
Number of subjects requiring mechanical ventilation or surfactant administration (nCPAP failure) but did not have a treatment interruption
Time frame: Randomization to 72 Hours Post Randomization
Population: Intent-to-Treat Without Treatment Interruption
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg/kg | nCPAP Failure Without Treatment Interruptions | 4 Participants |
| 75 mg/kg | nCPAP Failure Without Treatment Interruptions | 3 Participants |
| 100 mg/kg | nCPAP Failure Without Treatment Interruptions | 3 Participants |
| nCPAP Alone | nCPAP Failure Without Treatment Interruptions | 16 Participants |