Abstracts

There are very limited data on the treatment of juvenile myoclonic epilepsy (JME) from randomized clinical trials (RCT). We performed a sub-analysis of data among patients with JME who participated in a recently completed RCT. A randomized, double-blind, placebo-controlled, parallel-group study was conducted on lamotrigine (LAMICTAL^[reg], LTG) as adjunctive therapy in the the treatment of primary generalized tonic-clonic (PGTC) seizures in patients [ge] 2 years of age. Patients with a diagnosis of epilepsy with PGTC seizures who were receiving 1 or 2 antiepileptic drugs (AEDs) at study entry were eligible. Patients with partial seizures were carefully excluded. There were three study phases: Baseline; Escalation (7-12 weeks), during which study drug was titrated to a target dose; Maintenance, during which doses of study drug and concomitant AEDs were held constant for 12 weeks. A total of 121 patients were randomized, and 117 entered the dose escalation phase of the study; analysis of these data have been presented previously. Data on the 33 patients who met clinical diagnostic criteria for JME were analyzed by intent-to-treat methods and are now reported. 33 patients with JME (17 LTG, 16 placebo (PBO)) 2 to 52 years of age were randomized and received study drug. There was no significant difference between the JME patients randomized to LTG compared to those randomized to PBO by age, age at first generalized tonic-clonic seizure, or median seizures per month at screen. The median percent change from Baseline in PGTC seizure frequency (the primary efficacy endpoint) during the entire treatment period was a 72% decrease in the LTG group and a 16% decrease in the PBO group (p=0.020). During the entire treatment period a [underline][gt][/underline] 50% decrease in PGTCS frequency was achieved by 71% (12 of 17) in the LTG group and 31% (5 of 16) in the PBO group (p=0.038). For all seizure types, the median percent change from Baseline in seizure frequency during the entire treatment period was a 44% decrease in the LTG group and a 20% increase in the PBO group (p=0.011). The percent of patients in the LTG group with a [ge]50% increase in all seizures remained constant throughout the study (1/16; 6%). There was no difference in the number of patients who reported one or more adverse events (AE) between the LTG group (3/17; 18%) and the PBO group (3/16; 19%). Two patients from the LTG group (one an intentional carbamazepine overdose, and the second an episode of status epilepticus) and no patients from the PBO group discontinued the study prematurely due to an AE. Adjunctive LTG therapy was effective in the treatment of PGTC seizures, and was well-tolerated, among patients with JME. (Supported by GSK.)