Abstracts

Rationale: The number of concomitant antiepileptic drugs (AEDs) previously failed or currently taken by patients is often considered a measure of epilepsy severity. Post-hoc analyses from a recently completed randomized, placebo-controlled trial were conducted to assess the effect of the number of previously failed AEDs or the number of current concomitant AEDs on the efficacy of a new once-daily formulation of lamotrigine (LTG extended-release, LTG-XR) in subjects with intractable partial seizures with or without secondary generalization.Methods: LTG-naive patients (≥13 years) receiving a stable regimen of 1 or 2 AED(s) were enrolled in an 8-week Baseline phase. Patients having ≥8 partial seizures were randomized (1:1) to receive either LTG-XR or placebo (PBO). The treatment period consisted of Escalation (7 weeks) and Maintenance (12 weeks) phases with dosing based on background AEDs (inhibited, neutral or induced metabolism of LTG). The differences in the percent change in weekly seizure frequency from baseline were estimated using the Hodges Lehman test, and were compared between LTG-XR and PBO using Wilcoxon rank sum test for subgroups of patients who had previously failed 0, 1, 2 or ≥3 AED(s) prior to study entry (Comparison 1), and for subgroup of patients who were taking 1 or 2 concurrent AED(s) during the study (Comparison 2).Results: A total of 236 patients were randomized. Comparison 1: 51 patients failed zero AED (LTG-XR: n=20, PBO: n=31), 74 failed one AED (LTG-XR: n=38, PBO: n=36), 46 failed 2 AEDs (LTG-XR: n=28, PBO: n=18), and 65 failed 3 AEDs (LTG-XR: n=30, PBO: n=35). The LTG-XR vs. PBO differences in baseline-adjusted weekly seizure frequencies were: 9 (95% CI: -17 to 33), 15 (95% CI: -3 to 32), 30 (95% CI: 10 to 52) and 16 (95% CI: -1 to 32) for patients failing 0, 1, 2 or ≥3 AED(s), respectively. Comparison 2: 108 were taking 1 concomitant AED (LTG-XR: n=59, PBO: n=49) and 128 were taking ≥2 AEDs (LTG-XR: n=57, PBO: n=71). Baseline characteristics were similar between all treatment groups. The LTG-XR vs. PBO differences in baseline adjusted weekly seizure frequencies were: 12 (95% CI: -5 to 28), 23 (95% CI: 10 to 35) for patients with 1 and ≥2 AED(s), respectively. Tolerability results will be presented.Conclusions: Once daily LTG-XR is efficacious in patients with refractory partial epilepsy regardless of the number of previously failed AEDs prior to study entry or the number of current concomitant AEDs taken during the study.