Abstracts

Rationale: The FDA recently approved the extrapolation of efficacy obtained in adults with partial seizures to children aged ?-4 years for antiepileptic drugs (AEDs). This determination followed an analysis of data from studies in adults compared with trials in children. We used results from Phase III adolescent/adult registration studies (?-12 years of age) with PER in partial seizures (studies 304 [NCT00699972], 305 [NCT00699582], and 306 [NCT00700310]) and PGTCS in idiopathic generalized epilepsy (IGE; study 332 [NCT01393743]) to determine if age at epilepsy onset impacted treatment effect for adjunctive PER in both epilepsy syndromes. Methods: In studies 304, 305, and 306, pts with uncontrolled partial seizures despite 1?"3 AEDs were randomized to once-daily placebo, PER 8 or 12 mg (studies 304 and 305), or PER 2, 4, or 8 mg (study 306) during a 19-week Double-blind Treatment Phase (6-week Titration; 13-week Maintenance). In study 332, pts with PGTCS and IGE were randomized to once-daily placebo or PER 8 mg during a 17-week Double-blind Treatment Phase (4-week Titration; 13-week Maintenance). We assessed efficacy outcomes (percent change in seizure frequency per 28 days [baseline vs Double-blind Treatment Phase] and 50% responder rates [baseline vs Maintenance]) for partial seizures (pooled data from studies 304, 305, and 306) and PGTCS (study 332) according to age at diagnosis of epilepsy: < 12 vs ?-12 years. Age at diagnosis was also assessed as a categorical or continuous covariate. Results: Among pts with partial seizures receiving PER 2, 4, 8, and 12 mg/day, median percent change in seizure frequency was similar for < 12 years (-8.8 [n=96], -26.2 [n=91], -30.9% [n=233], -28.2 [n=138], respectively) and ?-12 years (-23.8 [n=84], -20.2% [n=80], -25.7% [n=197], -26.5 [n=115]) vs placebo (-13.0 [n=238] and -12.7 [n=203], respectively). 50% responder rates were also similar. Rank analysis of covariance and logistic regression indicated no effect of age at diagnosis on median percent change in seizure frequency or 50% responder rate, respectively, when age at diagnosis was treated as a categorical (P=0.9982/0.6017) or continuous variable (P=0.3620/0.3290). Among pts with PGTCS receiving PER 8 mg/day, median percent change in seizure frequency was similar for < 12 years (-78.3% [n=40]) and ?-12 years (-72.3% [n=41]) vs placebo (-39.5 [n=43] and -25.7 [n=38], respectively). Again, rank analysis of covariance and logistic regression indicated no effect of age at diagnosis on median percent change in seizure frequency or 50% responder rate when treated as a categorical (P=0.1933/0.7219) or continuous variable (P=0.1837/0.2760). Models for partial seizures and PGTCS studies included treatment, pre-randomization seizure frequency, and age at diagnosis as covariates. Conclusions: Based on this post-hoc analysis, there is no evidence to suggest substantial differences in the efficacy of adjunctive PER in pts with partial seizures or PGTCS who had a pediatric vs adult age at diagnosis. Funding: Eisai Inc.