Abstracts

RATIONALE: Refractory partial seizures are common in infants, and there are few proven treatment options. The safety and efficacy of lamotrigine (LTG) in this age group are currently being studied in a double-blind, placebo-controlled, responder-enriched trial. In this study, LTG is added to an ongoing antiepileptic drug (AED) regimen and titrated to an individually optimized dose. The titration and optimization phase of this study is open-label (OLP). Patients who [dsquote]respond[dsquote] to therapy with a [gt]= 40% and [lt]=80% seizure reduction are then eligible for randomization into a double-blind LTG continuation or withdrawal phase. The open label titration and optimization phase provides a preliminary view of the profile of LTG in this population.
METHODS: Infants with partial seizures, age 1-24 months, are entered into the study, and LTG (LAMICTAL) is gradually titrated to optimum effect consistent with product label (slower rate and lower final dose in the absence of enzyme-inducing AEDs (EIAEDs). The maximum allowed dose of LTG was 15.6 mg/kg/d (concurrent EIAEDs) or 5.1 mg/kg/day (no concurrent EIAEDs). The open-label phase of the study lasted up to 27 weeks.
RESULTS: 74 patients have completed or prematurely discontinued the OLP. The mean age is 13.5 months (SD 6.8, range 1-24). The mean weight is 9.7 kg (SD 3). There are 38 males and 36 females. The mean duration of epilepsy was 9.2 months (SD 6). Presenting seizure types were: partial seizures (81%, primarily noted as complex), secondarily generalized seizures (41%), and generalized seizures (31%). Data were available for efficacy analysis of 43 patients on EIAEDs and 18 patients on non-EIAEDs. Following titration and dose optimization, the mean total daily dose of LTG was 10.5 mg/kg/d (concurrent EIAEDs) and 3.4 mg/kg/d (non-EIAEDs), with ranges of 1.2-15.6 and 0.2-5.1 respectively. During the last 28 days of OLP, the median percent reduction from baseline seizure frequency was 35% for the EIAED group and 80% for the non-EIAED group. Forty-two percent of the patients on EIAEDs had a [gt]50% reduction from baseline seizure frequency compared to 67% of the patients on non-EIAEDs. 11 patients ( 18%) were seizure-free during the last 4 weeks of the OLP. There were 10 dermatologic reactions, 3 of which were attributable to concurrent infection, 6 were attributed to the medication. Rash was the cause of study drug discontinuation in 3 (4%) patients. There were no cases of Stevens-Johnson Syndrome or serious rash. Serious adverse events were systemic in nature or related to poor seizure control and in keeping with the overall ill nature of the patient population.
CONCLUSIONS: In this interim analysis, the data indicate that LTG is an effective and well-tolerated drug for patients with refractory partial seizures in the 1-24 month age range. This study is ongoing.
[Supported by: This study is being funded by GlaxoSmithKline]; (Disclosure: Salary - Glaxo SmithKline for: Womble, Caldwell, Onks, Morrison, Messenheimer, Blum, Consulting - J. Eric Pina-Garza, M.D. Consultant for Glaxo-Smith-Kline, Honoraria - J. Eric Pina-Garza, M.D. Speaker for Glaxo-Smith-Kline)