Abstracts

Rationale: Rufinamide is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome, a form of epilepsy with onset in childhood. Rufinamide is currently available only as a tablet formulation which may be difficult for some patients to swallow. Thus, a liquid (suspension) formulation has been developed. Methods: Three suspension formulations were produced using different homogenization speeds (1800, 2100 & 3000 rpm) and evaluated in a comparative bioavailability study alongside the tablet formulation. The study was an open-label, randomized, 4-sequence, 4-period crossover study comparing the rate and extent of systemic exposure of rufinamide as either a single 400 mg tablet or 10 mL (400 mg) of each of the 3 suspensions. Twenty-four healthy male or female volunteers were evaluated. ANCOVA was used to estimate differences between treatment means and associated 90% confidence intervals for ratios of log transformed rufinamide pharmacokinetic (PK) parameters AUC(0-72h), AUC(0-inf) and Cmax. Results: Bioequivalence was clearly demonstrated for all 3 suspension formulations with the currently marketed 400 mg tablet. Furthermore, each of the 3 suspensions were shown to be bioequivalent to each other (see Table). The extent of systemic exposure observed for the suspension and tablet formulations in this study was comparable to that seen in other studies. Of the 24 randomized subjects, 21 completed the study. Two subjects discontinued the study due to a non-treatment related AE (UTI) and one for an administrative error. Treatment-emergent AEs were mild or moderate in severity, with headache being the most commonly reported (38%). Conclusions: All 3 suspension formulations were bioequivalent to each other and to the currently marketed tablet formulation. Speed of homogenization appears to have no discernible effect on PK parameters within the range evaluated in this study (1800 to 3000 rpm). The safety profiles of rufinamide for the three suspension formulations and tablets formulation were comparable. Once approved for use, the suspension formulation may be used at the same doses as the currently marketed tablets and can offer a useful alternative for patients who have difficulty in swallowing tablets.