Abstracts

Rationale: There is little information in the literature regarding time to onset of response to antiepileptic drug (AED) therapy, especially with regard to specific subtypes of partial seizures, for example, secondarily generalized tonic-clonic (SGTCS). Some AEDs require slower titration to avoid associated toxicities, and time to efficacy is a concern, particularly for SGTCS, which may be disabling to patients. We examined time to onset of efficacy for patients with partial seizures treated with LTG-XR.Methods: This study was an international, multicenter, randomized, double-blind, placebo-controlled trial with the once daily formulation LTG-XR. LTG-naive patients (≥13 years old) with intractable partial seizures, 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 once-daily LTG-XR (LAMICTAL-XR) or placebo (PBO). The treatment period consisted of Escalation (7 weeks) and Maintenance (12 weeks) phases with dosing based on baseline AEDs (inhibited, neutral or induced metabolism of LTG). Time to ≥50% reduction was defined when a subject first achieved ≥50% reduction in seizure frequency and maintained response until end of treatment. Subjects who failed to meet this endpoint were censored at the date of last dose. Time to ≥50% reduction was analyzed using a two-sided log rank statistic using Kaplan-Meier methods. The likelihood that a subject could have no seizures in the first week is quite high. Data were censored for the first week in order to control for this 'by-chance' seizure occurrence. If the curves were statistically significant at 19 weeks (p<0.05), then the analysis was re-run, censoring at 18 weeks, 6 days. This process was followed iteratively until the p <0.05 and this was designated as the time to onset.Results: Of the 236 patients randomized, all patients had partial seizures (LTG-XR: n=116, PBO: n=120) and 93 had SGTCS (LTG-XR: n=46, PBO: n=47). Baseline characteristics were similar between all treatment groups. The percent of patients obtaining a ≥50% reduction in all partial seizures was 42% vs. 24% (LTG-XR vs. PBO, p=0.0037) with a time to onset of 18 days. The percent of patients obtaining a ≥50% reduction in SGTCS was 52% vs. 26% (LTG-XR vs. PBO, p=0.0292) with a time to onset of 13 days.Conclusions: There was a significant response to LTG-XR that occurred during the early escalation phase for all partial seizures and SGTCS.