Study Evaluating the Pharmacokinetics, Efficacy and Safety of Sildenafil in Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN) or Hypoxic Respiratory Failure and at Risk for PPH

• Conditions: Persistent Pulmonary Hypertension of the Newborn (PPHN) or Hypoxic Respiratory Failure and at Risk for PPHN; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2014-004166-23-Outside-EU/EEA
• Lead Sponsor: Pfizer, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-11
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Signed informed consent from legally acceptable guardian
2. PPHN or hypoxic respiratory failure associated with Idiopathic PPHN, Meconium aspiration syndrome, Respiratory distress syndrome, Sepsis, Pneumonia
3. Less than or equal to 72 hours of age
4. Greater than or equal to 34 week gestational age
5. Oxygenation index greater than or equal to (=)15 on 2 separate occasions calculated using blood gases taken at least 30 minutes apart prior to study drug infusion (Part1) or prior to randomization (Part 2)
Are the trial subjects under 18? yes
Number of subjects for this age range: 36
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior use of inhaled nitrogen oxide (iNO) for Part 2 only (Prior use of iNO is allowed for Part 1 )
2. Prior or immediate need for CPR (cardiopulmonary resuscitation) or ECMO (extracorporeal membrane oxygen)
3. Profound hypoxemia
4. Low pulmonary vascular resistance (PVR) as evidenced by large left to right intracardiac or ductal shunting based on the screening echocardiogram
5. Hypotension (mean arterial pressure [MAP] <35 mm Hg) or shock any time during screening
6. Life threatening or lethal congenital anomaly
7. Congenital heart disease exclusive of interatrial communication or patent ductus arteriosus
8. Lung hypoplasia syndromes diagnosed on the basis of prolonged oligohydramnios or hydrops fetalis
9. Congenital diaphragmatic hernia
10. Active seizures (within 12 hours of study drug infusion [Part 1] or randomization Part 2])
11. Apgar score of <3 at 5 minutes after birth
12. Bleeding diathesis
13. Receipt of any other experimental drug or device
14. Receipt of any prohibited concurrent medication/therapy at any time prior to randomization: Potent cytochrome P450 3A4 inhibitors (example, erythromycin, ketoconazole, itraconazole, and protease inhibitors), Ritonavir or Nicorandil, Endothelin antagonists (example tracleer, bosentan), Nitrates or Nitric Oxide (NO) donors in any form, except the prior or concurrent use of iNO. (subject would be eligible if nitroprusside was used, only if it was discontinued at least 2 hours prior to study drug infusion),Vasodilators (example alpha blockers, magnesium sulfate, calcium channel blockers, other phosphodiesterase inhibitors, prostacyclins, etc), excluding milrinone, which was allowed during as concurrent therapy, Supplemental arginine administered for the purpose of improving NO-dependent vasodilation. (maintenance quantities in total parental nutrition were allowed), Open-label sildenafil other than study drug.
15. Impairment of renal function (serum creatinine greater than [>] 2.5 × upper limit of normal [ULN]), hepatic function (Alanine Transferase [ALT] or Aspartate Amino Transferase [AST] > 3 × ULN or conjugated bilirubin > 2 × ULN), or haematological abnormalities: Severe anaemia (haemoglobin < 9 gram per decilitre [g/dl]), thrombocytopenia (platelets < 50,000 cells per micro millilitre [cells/mcl], or leucopenia (white blood cells < 2,500 cells/mcl) at the screening examination.
16. Known hereditary degenerative retinal disorders such as retinitis pigmentosa.
17. Symptoms of drug or alcohol related withdrawal.
18. Investigator’s discretion on a subject.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified