Abstracts

There is little information concerning the safety and efficacy of lamotrigine (LTG) in children younger than 2 years of age. We are evaluating the long-term safety of LTG in children with partial seizures in an ongoing, open-label, multicenter, international, continuation study (LAM20007). We report the preliminary safety results from this study. Subjects entering this study had completed either the open-label (OLP) or double-blind phases (DBP) of the primary study (LAM20006). In the primary study, subjects (age 1-24 months) with recurrent partial seizures receiving 1-2 anti-epileptic drugs (AEDs) were first entered into an OLP ([le] 27 weeks) where LTG was given as adjunctive therapy and was titrated, consistent with product labelling, to an individually optimized dose. Subjects with a [ge]40% reduction in seizure frequency from historical baseline were randomized into an 8-week DBP to either continue or gradually withdraw LTG with background AEDs continued. In this continuation study, LTG doses are titrated to optimal benefit with the option of withdrawal to LTG monotherapy. Subjects are treated for 48 weeks or until their second birthday, whichever occurs later. Demographic and safety data were available for 96 subjects (52% male; mean age, 16.8 months; mean weight, 10.5 kg). Sixty-eight percent of subjects received enzyme-inducing AEDs (EIAEDs). Sixty-seven (70%) subjects were exposed to LTG for [ge]48 weeks. The median of the modal total daily dose was 11.8mg/kg/day (range 0.9-30.7) for the EIAED group and 4.8mg/kg/day (range 0.2-15.4) for the non-EIAED group. The most common adverse events (AEs) ([ge]20% of subjects) were mostly mild to moderate in intensity and consisted of pyrexia (43%), upper respiratory tract infection (26%), cough (26%), ear infection (25%), and vomiting (21%). AEs caused 11 subjects to discontinue the study. Rash was reported for 15 subjects (16%), caused one subject to discontinue study drug, and occurred more frequently in the EIAED group (25%) than in the non-EIAED group (4%). Rash was considered to be a serious AE (SAE) for one subject but was not considered to be LTG-related and did not require discontinuation of LTG. The most frequent ([ge]5% of subjects) SAEs were convulsion (13%), status epilepticus (7%), pneumonia (6%), and pyrexia (5%). Six subjects died during the study; none of the deaths was considered to be LTG-related. This preliminary analysis indicates that LTG is a well-tolerated long-term treatment in infants with recurrent partial seizures. (Supported by GlaxoSmithKline)