Abstracts

Rationale: In most cases, using the Last Observation Carried Forward (LOCF) analysis produces a higher rate of seizure freedom than does a completer analysis. Another intent-to-treat analysis might be a more realistic approach where dropouts cannot be counted as seizure free, the Pragmatic Intent-to-Treat (Gazzola, Epilepsia 2007). 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 or older) with intractable partial seizures, receiving a stable regimen of 1 or 2 AED(s) were enrolled in an 8-week baseline phase. Patients having at least 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 concurrent AED(s) (inhibited, neutral or induced metabolism of LTG). The Pragmatic Intent-to-Treat was used to summarize seizure free patients during the Maintenance phase whereby patients that did not complete the study could not be considered seizure free. Statistical analysis was performed with the Fisher’s exact test. Results: 236 patients were randomized and included in the Pragmatic Intent-to-Treat population (LTG-XR: n=116, PBO: n=120). Baseline characteristics were similar between treatment groups. The seizure free rate during the Maintenance phase using the Pragmatic Intent-to-Treat was 14% vs. 3% (LTG-XR vs. PBO, p=0.0015). The median maintenance phase daily doses of LTG-XR for the inhibited, neutral and induced groups were 200 mg, 300 mg and 500 mg, respectively. The most common (over 5%) drug-related adverse events for LTG-XR and PBO respectively were dizziness (16% vs 2%), headache (8% vs 3%) and somnolence (6% vs 3%). Non-serious rash rate was 2% for LTG-XR and 1% for PBO. No serious rash was reported. Conclusions: Once daily LTG-XR is efficacious in patients with refractory partial seizures even when using the more conservative analysis method of the Pragmatic Intent-to-Treat.