Abstracts

Rationale: To use the combined escalation and maintenance phase results from two similar trials evaluating lamotrigine (LTG) as monotherapy for newly-diagnosed absence epilepsy to derive an estimated response rate for achieving and maintaining efficacy. Methods: Both trials of LTG in newly-diagnosed absence epilepsy used an open-label titration-to-effect design. US44 (Frank et al, Epilepsia 1999; 41:357-359) also had a 4-week double-blind withdrawal phase for responders following the dose-escalation phase, while LAM100118 (Holmes et al, Epilepsy Res 2008; 82 (2-3):124-132) utilized a 12-week open-label maintenance period open only to the responders from the dose escalation phase. Both studies defined responder as achieving complete seizure control as confirmed by hyperventilation electroencephalogram (HV-EEG). Data from the escalation phases were combined to determine efficacy in escalation. Maintenance of efficacy was derived by combining the results from subjects randomized in US44 to remain on LTG with the results from the maintenance phase of LAM100118. This maintenance rate was combined with the escalation rate to derive an estimated response rate for achieving and maintaining efficacy. Results: A total of 60/99 (60%) of subjects achieved complete seizure control by HV-EEG during the escalation phase when the data from both studies were combined. Nine (9) of 14 (64%) subjects in US44 randomized to continue to receive LTG and 21 of 27 (78%) subjects who continued in the maintenance phase of LAM100118 remained seizure-free for a combined result of 30/41 (73%). Combining this maintenance rate with the seizure-free rate during escalation (60% x 73%) yields a rate of 44% for achieved and maintained seizure freedom. The rate of adverse events reports considered to be drug-related was similar in each of the two studies. In study US44, 37% of subjects reported a potentially drug-related adverse event compared with 26% in LAM100118. The most common (reported by at least 5% of subjects) drug-related adverse events were abdominal pain (11%), nausea (6%), and dizziness (6%) in US44 and headache (9%) and psychomotor hyperactivity (7%) in LAM100118. Conclusions: LTG is an effective monotherapy treatment for newly-diagnosed absence seizures with an expected overall maintenance of complete response rate of 44%. LTG was well tolerated in both studies without occurrence of serious rash.