Abstracts

Rationale: LAM30055 is a recently-concluded study of lamotrigine for monotherapy of partial seizures using historic data as control. Study 105-30/31 was one of the studies making up the historic control database. We have compared these studies for the escape endpoint and for safety. Methods: Both studies utilized similar subject populations and the same Escape Criteria. Subjects experienced at least 4 partial seizures during an 8-week baseline while receiving AED monotherapy. In 105-30/31, the background AED was enzyme-inducing AEDs (EIAEDs) carbamazepine (CBZ) or phenytoin (PHT). In LAM30055, the background AED was valproate (VPA) or a non-EIAED. Low-dose VPA or lamotrigine, as LAMICTAL immediate-release (LTG IR; 105-030/031) or lamotrigine extended-release (LTG XR, 250 or 300 mg/day; LAM30055), was escalated and the background AED withdrawn. This was followed by 12 weeks of LTG IR or LTG XR monotherapy. The proportion of subjects meeting Escape Criteria was compared in subjects who began withdrawal of the background AED. Results: Study populations were similar with respect to age, gender and ethnicity. Baseline seizure frequency was higher in 105-30/31 (2.3/week vs 1.4 and 1.5 for 300 mg/day and 250 mg/day, respectively). Forty-four percent of lamotrigine-treated subjects met an Escape Criterion in 105-30/31 compared to 12% and 16% for the 300 mg/day and 250 mg/day groups, respectively, in LAM30055. In comparison, 80% of subjects who were converted to low-dose VPA in 105-30/31 met an Escape Criterion, and an aggregate of 86% of subjects escaped in the historic database. In 105-30/31, subjects escaped primarily during withdrawal of the background EIAED. In LAM30055, escapes occurred primarily in the monotherapy phase. Possible reasons for the better response in LAM30055 will be discussed and include possible pharmacodynamic interactions with the background AED, particularly CBZ and PHT in 105-30/31. The majority (83% in 105 30/31 and ~57% in LAM30055) of subjects reported at least 1 AE. Dizziness, nausea and headache (105-30/31), and headache, dizziness and rash (LAM30055) were the most frequently reported. SAEs were reported by 5% of subjects in 105-30/31 and 4% of subjects in LAM30055. There were no deaths with lamotrigine treatment in either study. 20% of subjects in 105-30/31 withdrew due to AE compared to 7% in LAM30055. Rash (4%) was the most frequent reason for discontinuation in both studies. Conclusions: The proportion of subjects meeting Escape Criteria was substantially lower in LAM30055 compared to 105-30/31. The timing of escape was also different between the two studies; however, both LTG IR and LTG XR were efficacious as conversion monotherapy. AE profile was similar in both studies, but tolerability was better in LAM30055.