Abstracts

Rationale: There is little information concerning the safety and efficacy of lamotrigine (LTG) in children younger than 2 years of age. We evaluated the long-term safety of LTG in children with partial seizures in an open-label, multicenter, international, study (LAM20007). We previously reported the preliminary safety results from this study and now report the final data.Methods: Subjects entering this study had either been treated with LTG in the primary study (LAM20006) or were LTG-naïve subjects (age 1-24 months) with recurrent partial seizures receiving 1-2 anti-epileptic drugs (AEDs). LTG was given as adjunctive therapy and titrated according to metabolic induction status (induced vs. VPA/non-induced) to an individually optimized dose with the option of withdrawal to LTG monotherapy. Subjects were treated for 48 weeks or until their second birthday, whichever occurred later.Results: 204 subjects comprised the safety population. (90 female, 114 male; mean age, 15.9 months; mean weight, 9.5 kg). Fifty-nine percent of subjects received concurrent enzyme-inducing AEDs. Seventy percent of subjects were exposed to LTG for >48 weeks. The median of the average total daily dose was 10.8mg/kg/day (range 0.9-28.1) for the induced group 4.0mg/kg/day (range 0.1-15.7) for the non-induced group, and 3.9mg/kg/day (range 1.0-6.5) for subjects receiving VPA only. The most common adverse events (AEs) (>15% of subjects) were mostly mild to moderate in intensity and consisted of pyrexia (45%), upper respiratory tract infection (28%), ear infection (22%), cough (19%), vomiting (18%), irritability (17%), otitis media (17%), and constipation (16%). Rash was reported for 13% of subjects. Rash was a serious AE (SAE) for one subject but was not LTG-related and the subject continued to receive LTG. There were no cases of serious rash defined as rash associated with hospitalization and the discontinuation of LTG or rash reported to be Stevens Johnson Syndrome or toxic epidermal necrolysis. Adverse events caused 18 subjects to discontinue the study. The most frequent (>5% of subjects) SAEs were pneumonia (8%), complex partial seizures (6%) and status epilepticus (6%). Seven subjects died during the study; none of the deaths was considered to be LTG-related. Twenty-two subjects experienced 23 treatment-emergent clinically significant ECG abnormalities. There were few clinically meaningful treatment-emergent changes in clinical laboratory or neurological evaluations throughout the study.Conclusions: This final analysis further supports the preliminary findings that LTG is a well-tolerated long-term treatment in infants with recurrent partial seizures.