Abstracts

Rationale: Adjunctive perampanel, an oral, non-competitive AMPA receptor antagonist, reduced the frequency of refractory partial seizures compared with placebo in three Phase III trials (studies 304 [NCT00699972]; 305 [NCT00699582]; 306 [NCT00700310]). Primary data from these trials are reported elsewhere (French et al. Annual Meeting of the American Academy of Neurology [AAN] 2011: Abstract LBS.002; French et al. Epilepsia 2011; 52 [Suppl 6]: 10; Krauss et al. Neurology 2012; 78: 1408-1415). Here, data were pooled to explore changes in seizure frequency by seizure type and concomitant AEDs. Methods: Patients (≥12 years), with partial seizures despite receiving 1-3 AEDs, were randomized to once-daily placebo, perampanel 8 or 12 mg (studies 304 and 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Trials included a 6-week Baseline Period and a Double-blind Treatment Phase (6-week Titration; 13-week Maintenance). Patients recorded the number of partial seizures and their types (simple partial seizures with/without motor signs, complex partial [CP] seizures, and CP seizures with secondary generalization [SG seizures]) daily in a diary. Investigators reviewed the diaries with patients to ensure correct seizure classification. Median percentage changes in the frequencies of all partial seizures, CP plus SG (CP+SG) seizures, and SG seizures only (Baseline vs Double-blind Phase), were analyzed in the intent-to-treat (ITT) analysis set (all randomized and treated patients with any seizure data), and also according to the most common concomitant AEDs at Baseline. P-values are presented to highlight effects of interest for these analyses; they are not adjusted for multiplicity and the data for the subgroups may overlap. Results: The ITT analysis set included 1478 patients from studies 304 (n=387), 305 (n=386), and 306 (n=705). At Baseline, most patients were receiving ≥2 concomitant AEDs (1, n=206; 2, n=751; 3, n=522): the most common were carbamazepine (n=491; 33.2%), valproic acid (n=478; 32.3%), lamotrigine (n=458; 31.0%), and levetiracetam (n=435; 29.4%). Median reductions in the frequencies of all partial seizures, CP+SG seizures, and SG seizures were greater with perampanel 4-12 mg than placebo, in the overall population (Table 1; p<0.01, all comparisons) and in subgroups of patients receiving any of the 4 most common AEDs (Table 2; statistical significance not evaluated). Conclusions: In this analysis of Phase III data by randomized dose, adjunctive perampanel reduced the frequency of different types of partial seizures, including SG seizures, compared with placebo; results were consistent in patients receiving any of the 4 most commonly co-administered AEDs. Additional analyses based on both actual dose and within-patient responses have shown a benefit of perampanel 12 mg over 8 mg (Kramer et al. AAN 2012: Abstract P06.117). Support: Eisai Inc