Objective: Clobazam oral soluble film (COSF) is a novel dosage form under development for the adjunctive treatment of seizures associated with Lennox?Gastaut syndrome. The present study was undertaken to assess the pharmacokinetics of clobazam administered as single doses of COSF 20 and 10 mg compared with clobazam tablets (CTAB) 20 and 10 mg in healthy adults. A secondary objective was to assess the safety and tolerability of single doses of COSF 20 and 10 mg.
Methods: A total of 51 adult volunteers were enrolled in a single?dose, open?label, randomized four?sequence, four?period, crossover study with treatments (A) COSF 20 mg, (B) CTAB 20 mg, (C) COSF 10 mg, and (D) CTAB 10 mg. Pharmacokinetic sampling for clobazam and N?desmethylclobazam was carried out until 21 days postdose with a 28?day washout. Subjects were monitored for adverse events (AEs) throughout the study. Visual inspections of the administration site were performed before and after COSF administration to monitor for mucosal irritation.
Results: COSF at single doses of 10 and 20 mg was bioequivalent to CTAB at equivalent doses for both clobazam and its active metabolite N?desmethylclobazam. The pharmacokinetics of both formulations was dose?proportional at doses of 10 and 20 mg. The number of AEs and the number of subjects experiencing AEs were dose?related across the treatment groups, with somnolence the most common event. None of these events was severe or serious, and most were mild. There was no evidence for local irritation at the administration site following COSF.
Significance: COSF is a novel clobazam dosage form that is bioequivalent to CTAB. Because of its ease of administration, COSF may be expected to improve adherence, reduce likelihood of dosing error, and provide more accurate dosing than formulations of clobazam that are currently available.