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摘要
Background: Lacosamide, a new antiepileptic drug (AED) with a different pharmacological action that enhances sodium channel slow inactivation, is approved for the adjunctive treatment of partial-onset seizures in adults. Previous analyses of pooled phase II/III trials have demonstrated that lacosamide provides additional efficacy when added to a broad range of AEDs.
Objective: To further evaluate the efficacy and safety of lacosamide by grouping patients based upon the sodium channel-blocking properties of their concomitant AEDs.
Study Design: Post hoc exploratory analyses were performed on pooled data in which patients were grouped based upon inclusion or non-inclusion of at least one 'traditional' sodium channel-blocking AED (defined as carbamazepine, lamotrigine, oxcarbazepine and phenytoin derivatives) as part of their concomitant AED regimen.
Setting: Data pooled from previously conducted phase II/III clinical trials of lacosamide.
Patients: Adult patients with partial-onset seizures with or without secondary generalization (N = 1308).
Intervention: Four- to six-week Titration Phase followed by 12-week maintenance treatment with adjunctive lacosamide (Vimpat (R)) [200, 400 or 600 mg/day] or placebo.
Main Outcome Measure: Efficacy variables included change in seizure frequency per 28 days and the proportion of patients experiencing a >= 50% reduction in seizure frequency (50% responder rate) from Baseline to the Maintenance Phase. The proportion of patients experiencing a >= 75% reduction in seizure frequency from Baseline to the Maintenance Phase (75% responder rate) was also assessed. Safety parameters assessed were treatment-emergent adverse events (TEAEs) and discontinuation due to TEAEs. Additional safety assessments were changes in ECG and laboratory parameters as well as vital signs (including bodyweight).
Results: Of 1308 patients in the pooled phase II/III population, the majority (82%) were using at least one 'traditional' sodium channel-blocking concomitant AED. In this subgroup of patients, adjunctive lacosamide showed significant reductions in seizure frequency (p < 0.01, all dosages) and significantly greater 50% and 75% responder rates (p < 0.01 for 400 mg/day; p < 0.01 [50% responder rate] and p < 0.05 [75% responder rate] for 600 mg/day) compared with placebo; these effects were similar to the results seen in the pooled phase II/III population. TEAEs and discontinuations due to TEAEs in this subgroup were dose related and similar to the pooled phase II/III population. In the remaining subgroup of patients, i.e. those not taking 'traditional' sodium channel-blocking AEDs as part of their concomitant AED regimen (n = 231; 18%), a pronounced, dose-related seizure reduction was observed with lacosamide (p < 0.01, 400 and 600 mg/day for median percent seizure reduction and 50% or 75% responder rates). Also in this group, incidences of TEAEs were low, and discontinuations due to TEAEs did not appear to increase with dose. Analyses of ECG, laboratory and vital signs (including bodyweight) assessments did not identify abnormalities in either subgroup that were outside of the known safety profile of lacosamide observed in the pooled phase II/III population.
Conclusion: In this post hoc exploratory analysis, adjunctive lacosamide demonstrated significant seizure reduction over placebo regardless of the inclusion of 'traditional' sodium channel blockers in the concomitant AED regimen. Future prospective studies evaluating single AED combinations (e.g. lacosamide plus one other drug) are needed to better evaluate the potential for additive or synergistic effects of lacosamide in combination with AEDs not considered 'traditional' sodium channel blockers.
- 出版日期2010
