Abstracts

Rationale: In Canada perampanel is indicated as an adjunctive therapy for the management of partial-onset seizures, in adult patients with epilepsy who are not satisfactorily controlled with conventional therapy. Canadian patients were able to continue treatment with perampanel accessed through the named patient Special Access Programme (SAP), which allows practitioners to request access to drugs unavailable for sale. We present the efficacy and safety of perampanel for over 3 years in 9 subjects currently treated at Canadian centers, who previously completed the Phase III studies. They were eligible to enter an open-label Phase III extension study Methods: Perampanel is a noncompetitive -amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist. Patients aged 12 years of age with treatment-resistant partial-onset seizures (with/without secondary generalization) receiving ongoing treatment with stable doses of 1 3 approved antiepileptic drugs (AEDs) were enrolled in study 304 to assess efficacy and safety of once-daily perampanel 8 mg, 12 mg vs. placebo, added to 1-3 concomitant antiepileptic drugs (AEDs) . Study completers could continue in the extension study 307 titrated to their individual maximum tolerated perampanel dose ( 12 mg/day) was followed by open label maintenance. Canadian completers of study 307 who benefitted on the drug continued to receive perampanel through SAP. Efficacy was based on the Engel classification of seizure outcomes and on seizure frequency per 28 days Changes in the dose of perampanel and concomitant AED use were assessed, as were treatment-emergent adverse events and relevant changes in laboratory values Results: In October 2012, 8 patients who completed study 304/307 and one patient who completed study 306/307 and relocated to Canada, received perampanel through the SAP on a maintenance dose of 4 mg/day (n=1), 6 mg/day (n=1) and 12 mg/day (n=7). The mean age is 36.7years (min,max 16,63). The mean duration of treatment with perampanel is 3.7 years (min,max 3.1,4.1). In 307 real-life experience 4 patients had no adverse events, mild dizziness in 1, mild weight loss in 1 and seizure related falls in 1 patient. Adverse event report was not available in 1 patient. Two patients were assessed as class I (seizure free or non disabling), 5 were class II (rare disabling seizures), and one was Engel class IV (no improvement) Conclusions: Except for 1 patient the other 8 demonstrated significant or worthwhile improvement at last visit based on Engel classification. Perampanel was well tolerated in these 9 patients. The majority of the treatment emergent adverse events were mild to moderate in severity, with dizziness being reported most frequently. Real world perampanel efficacy and safety over 3 years was consistent with the efficacy and safety profile of perampanel seen in the core Phase III studies and in the long-term Phase III extension study.