Thirty subjects will be enrolled in a dose escalation study. Subjects 1-10 will receive melatonin (0.5 mg/kg). If that dose proves to be safe, subjects 11-20 will receive an increased dose of melatonin (3 mg/kg). Subjects 21-30 will receive a dose increased to the targeted projected therapeutic dose (5 mg/kg).
The serum concentration of melatonin and capture adverse event reports during this dose escalation study in neonates undergoing hypothermia and the long-term safety and potential efficacy via developmental follow-up performed at 18-22 months of age. In addition, this study will determine the effect of melatonin on the inflammatory cascade, oxidative stress, free radical production, and serum biomarkers of brain injury in neonates undergoing hypothermia.
