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FDA Accepts Resubmission of New Drug Application for IV Carbamazepine for Epilepsy
The FDA has accepted for review the resubmission of a new drug application for Carnexiv (Lundbeck), an intravenous (IV) formulation of the antiepileptic drug carbamazepine. An action letter is anticipated before the end of 2016. The resubmission was in reply to a complete response letter from the FDA issued in 2014 requesting additional data regarding the chemistry, manufacturing, and controls (CMC) of the product. The proposed U.S. trade name, Carnexiv, is under consideration with the FDA as well.
Oral carbamazepine is an important treatment option for people with epilepsy, but some patients are unable to take the medication by mouth. IV carbamazepine received an orphan drug designation from the FDA in 2013 and is proposed for use as replacement therapy in adults who are receiving a stable maintenance oral dose of carbamazepine to control certain seizure types, when oral carbamazepine administration is temporarily not feasible.
In a Lundbeck-supported study, investigators analyzed pooled tolerability findings and the maintenance of seizure control with IV carbamazepine in a phase 1 open-label trial and a phase 3 trial. Patients receiving a stable oral dosage of carbamazepine were switched to an IV formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15-minute or a 30-minute infusion every six hours for up to seven days, and were then switched back. A subset of patients who tolerated 15-minute infusions also received two- to five-minute (rapid) infusions. Clinical assessments included physical and laboratory evaluations, electrocardiography, and adverse event monitoring for tolerability.
Of the 203 patients exposed to IV carbamazepine (30 minutes, n = 43; 15 minutes, n = 160), 113 received 149 rapid infusions. During infusion, the most common adverse events included dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac adverse events. The tolerability profile of IV carbamazepine appeared to be similar between patients who received less than 1,600 mg per day (n = 174) of IV carbamazepine and those who received greater than or equal to 1,600 mg per day (n = 29). Seizure control was maintained as patients transitioned between oral and IV carbamazepine.
Sources: Lundbeck; April 22, 2016; and Epilepsia; April 25, 2015.