A Clinical Trial Assessing the Efficacy and Safety of a New Injectable Formula of Sodium Phenobarbital Containing No Additives for the Treatment of Neonatal Seizures

Abstract

Aims：A new phenobarbital preparation for injection containing no additives（NOBELBAR® ）was developed in Japan for safer use in neonates with seizures. This study was conducted to evaluate the clinical efficacy and safety of NOBELBAR®for the treatment of neonatal seizures. Methods：This investigator-initiated clinical trial was an open-label, uncontrolled, multicenter study, conducted in compliance with the good clinical practice. Phenobarbital was initially administered intravenously at a loading ／ ／ dose of 20 mg／kg. An additional dose of 20 mg／kg was given if the seizures did not resolve. The primary efficacy was evaluated 30 minutes after the administration of the loading dose. Infants who responded to the loading ／ administration received maintenance therapy with 2.5 to 5 mg／kg intravenous phenobarbital once daily for 6 days. Results：NOBELBAR®was administered to 10 neonates with seizures. The primary efficacy was evaluated as complete response in all patients. Adverse events were reported in 9 of the 10 patients（90％), most of which ／ were mild. Plasma phenobarbital concentrations ranged from 18.7 to 45.3 mg／mL. Conclusion：The study demonstrated that NOBELBAR®was effective for the control of neonatal seizures, and plasma drug concentrations were maintained within the therapeutic range. Approved for manufacturing and marketing was obtained based on the results of this study and other relevant data. （Clinical Trials. number, UMIN-C000000410, JMA-ⅡA00002.)

Neonatal Formulations: The Need for a Tailored, Knowledge Driven Approach

“…This confirms the Belgian observation on the difficulties to retrieve the exact amounts of propylene glycol in intravenous phenobarbital formulations administered to newborns [12]. Moreover, it turned out that there are also parabens/sodium metabisulphite free gentamicin formulations and even propylene glycol free phenobarbital formulations available in some specific countries or regions [14,15,50].…”