Abstracts

Rationale: In most cases, using the Last Observation Carried Forward analysis produces a higher proportion of seizure freedom than does a completer analysis. The Pragmatic Intent-to-Treat (P-ITT) analysis, where dropouts are not counted as seizure free, might be a more realistic approach. Methods: Three international, multicenter, double-blind, randomized epilepsy trials have been completed evaluating once daily lamotrigine extended-release (LTG-XR) in patients >= 13 years of age: two double-blind, placebo-controlled adjunctive studies, one for intractable partial seizures (LAM100034) and one for PGTC seizures (LAM100036), and one conversion to monotherapy trial for partial seizures (LAM30055). The treatment period for LAM100034 and LAM100036 consisted of Escalation (7 weeks) and Maintenance (12 weeks) and for LAM30055 consisted of Conversion (10-11 weeks) and Monotherapy (12 weeks, 250mg/day or 300mg/day). The P-ITT was used to summarize seizure free patients during Maintenance or Monotherapy whereby patients who did not complete the study were not considered seizure free. Statistical analysis was performed using the Fisher’s exact test. Results: The P-ITT population contained 236 patients (LTG-XR: n=116, PBO: n=120) from LAM100034, 143 patients (LTG-XR: n=70, PBO: n=73) from LAM100036, and 223 patients (LTG-XR 300mg/day: n=112, LTG-XR 250mg/day: n=111) from LAM30055. Baseline characteristics were similar for all treatment groups. The seizure free rate during the Maintenance/Monotherapy phase using the P-ITT for LAM100034 was 14% vs 3% (LTG-XR vs PBO, p=0.0015), for LAM100036 was 44% vs 12% (LTG-XR vs PBO, p=<0.0001), and for LAM30055 was 19% and 10% (LTG-XR 300mg/day and LTG-XR 250mg/day). The responder rate for 50% reduction in seizure frequency during the Maintenance/Monotherapy phase using the P-ITT for LAM100034 was 50% vs 28% (LTG-XR vs PBO, p=0.0004), for LAM100036 was 70% vs 38% (LTG-XR vs PBO, p=0.0002), and for LAM30055 was 57% and 43% (LTG-XR 300mg/day and LTG-XR 250mg/day). The most common drug-related adverse events (AEs) for LTG-XR and PBO respectively in LAM100034 were dizziness (16% vs 2%), headache (8% vs 3%) and somnolence (6% vs 3%) and in LAM100036 were dizziness (3% vs 0%) and rash (3% vs 0%). The most common drug-related AEs in LAM30055 for LTG-XR 300mg/day and LTG-XR 250mg/day respectively were headache (6% and 8%), dizziness (5% and 7%), rash (4% and 9%) and nausea (3% and 5%).