Abstracts

Rationale: This abstract reports long term safety results from the 3 controlled clinical trials with once-daily lamotrigine extended-release (LTG XR) as adjunctive therapy in patients with partial or primary generalized tonic-clonic seizures and conversion to monotherapy. LTG XR allows a reduction in daily trough-to-peak fluctuations in LTG serum concentrations compared to LAM IR [Epilepsia 2008, 49(3):410-417] and may improve compliance due to once-daily as opposed to twice-daily dosing. Methods: 3 international, multicenter, double-blind, randomized epilepsy trials have been completed with LTG XR in patients ≥ 13 years of age: a double-blind, placebo-controlled adjunctive studies for intractable partial seizures (LAM100034) and a PGTC seizures (LAM100036), and a conversion to monotherapy trial for partial seizures (LAM30055). The treatment period for LAM100034 and LAM100036 consisted of Escalation (7 weeks), Maintenance (12 weeks) and open-label Continuation (48 weeks), and for LAM30055 Conversion (10-11 weeks), Monotherapy (12 weeks, 250mg/day or 300mg/day) and open-label Continuation (48 weeks). Results: Demography: A total of 662 patients were treated with LTG XR in these 3 studies. The median age of patients treated was 32 years. The majority of the patients (92%) were between 16 and 65 years of age. Forty patients (6%) were <16 years of age and 13 patients (2%) were >65 years of age. Approximately equal numbers of female (52%) and male (48%) patients participated. Exposure: The majority of the patients (83%) were exposed to LTG XR for ≥26 weeks. In the 3 modal-dose groups analyzed, the numbers of patients who were exposed to LTG XR for ≥26 weeks were 143 (66%) in the <300 mg/day group, 245 (91%) in the ≥300 to <500 mg/day group, and 158 (90%) in the ≥500 mg/day group. The number of patients who were exposed to LTG XR for at least 52 weeks were 270 (41%), or 94 (43%) in the <300 mg/day group, 59 (22%) in the ≥300 to <500 mg/day group, and 117 (67%) in the ≥500 mg/day group. Adverse events (AE): 455 patients (69%) reported at least 1 treatment-emergent AE (TEAE). The 5 most common TEAEs were headache (25%) dizziness (16%), nausea (8%), vomiting (7%) and nasopharyngitis (7%); 202 (31%) patients reported at least 1 TEAE considered to be reasonably attributable to LTG XR. The 5 most common drug-related TEAEs were dizziness (10%) headache (6%), somnolence (4%), nausea (4%) and all rash (4%). Treatment-emergent serious AEs (TESAEs) were reported by 43 patients (6%); TESAEs were reported by 2 patients for ataxia, dizziness, grand mal convulsion, nystagmus, partial seizures with secondary generalization, status epilepticus, and vomiting; no other TESAEs were reported by more than 1 patient. Conclusions: The AE profile for LTG XR was similar in type and frequency to the established AE profile for LTG IR tablets.