A MULTI-CENTRE, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, TWO-ARMED, PARALLEL GROUP STUDY TO EVALUATE EFFICACY AND SAFETY OF IV SILDENAFIL IN THE TREATMENT OF NEONATES WITH PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN) OR HYPOXIC RESPIRATORY FAILURE AND AT RISK FOR PPHN, WITH A LONG TERM FOLLOW-UP INVESTIGATION OF DEVELOPMENTAL PROGRESS 12 AND 24 MONTHS AFTER COMPLETION OF STUDY TREATMENT

简要总结

主要结局

次要结局

• Percentage of Participants With Individual Components of Treatment Failure(14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days))
• Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion(Baseline, Hours 6, 12 and 24 after start of infusion)
• Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure(14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days))
• Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion(Baseline, Hours 6, 12 and 24 after start of infusion)
• Total Plasma Clearance (CL) of Sildenafil and Its Metabolite(Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1)
• Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite(Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1)
• Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation(14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days))
• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 31 days after end of study drug infusion (up to 45 days))
• Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Number of Participants With Laboratory Abnormalities(Up to 14 days from initiation of study drug infusion)
• Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)(Month 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24(Baseline, Hours 6, 12 and 24 after start of infusion)
• Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite(Loading dose, Day 1: prior to the start of infusion, 5, 30 minutes after end of loading infusion; Maintenance dose: 48 to 72, 96 to 120 hours during infusion and immediately prior to end of maintenance infusion (up to maximum on Day 14))
• Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Number of Treatment-Emergent Adverse Events (AEs) According to Severity(Baseline up to 31 days after end of study drug infusion (up to 45 days))
• Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths(up to 24 months after end of study treatment in Part A (maximum up to 26 months))
• Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))
• Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score(Month 12 and 24 after end of study treatment in Part A (Day 1 to 14))