Abstracts

Rationale: Lacosamide is an antiepileptic drug approved for adjunctive treatment of partial-onset seizures (POS) in adults. This is the first assessment of the safety of adjunctive lacosamide for uncontrolled primary generalized tonic-clonic seizures (PGTCS) in adults with idiopathic generalized epilepsy. Methods: This was a Phase 2, multicenter, open-label pilot study (SP0961) comprised of a 4-week prospective Baseline, followed by 3-week Titration and 6-week Maintenance phases. Dose titration started at 100mg/day (50mg bid) and increased weekly to a maximum of 400mg/day. Primary variables were change in number of seizure days/28 days from prospective Baseline to Maintenance for absence and myoclonic seizures. Other variables were percent change from prospective Baseline in number of seizure days/28 days for absence and myoclonic seizures, percent change from combined Baseline (12-week retrospective period + 4-week prospective Baseline) in 28-day seizure frequency for PGTC seizures, changes in count of generalized and 3Hz spike-wave discharges on 24-hour ambulatory EEG, treatment-emergent adverse events (TEAEs) and withdrawals due to TEAEs. Results: Of 49 patients enrolled (mean age 29.7 years, 73.5% female), 40 (81.6%) completed the study. A majority (69.4%) were taking 2-3 concomitant AEDs at baseline. All had a history of tonic-clonic seizures; 69.4% and 55.1% had a history of absence and myoclonic seizures, respectively. At prospective Baseline, mean absence and myoclonic seizure days/28 days were 4.7±8.48 and 4.7±7.98, respectively. For absence seizures, mean change from prospective Baseline was 0.26±3.67 to Titration and -0.37±4.80 to Maintenance, corresponding to a mean percent change of -10.63±76.3 to Maintenance. For myoclonic seizures, mean change from prospective Baseline was -1.29±6.26 to Titration and -2.19±5.80 to Maintenance; mean percent change to Maintenance was -44.95±73.9. Mean percent change (combined Baseline to Maintenance) was -26.37±156.16 for PGTC 28-day seizure frequency; 29 (59.2%) patients did not have tonic-clonic seizures during Maintenance. Frequently reported TEAEs (>15%) were dizziness (19 patients [38.8%]), nausea (13 [26.5%]), headache (8 [16.3%]), and somnolence (8 [16.3%]). One patient experienced a serious TEAE of "petit mal status", though EEG indicated nonspecific diffuse cortical dysfunction with possible nonconvulsive status epilepticus. Nine (18.4%) patients discontinued early: 5 (10.2%) due to a TEAE, 4 (8.2%) withdrew consent. There was no consistent correlation between changes in EEG discharges and clinical outcome. Conclusions: Adjunctive lacosamide appears to be safe in this population in that it did not systematically worsen either absence or myoclonus, though a small subset of patients may have had an increase in absence seizures. Reductions in PGTC seizure frequency were observed. TEAEs were similar to those observed among patients with POS treated with adjunctive lacosamide, except for seizure-related events. Results of this pilot trial support further evaluation of lacosamide for treatment of PGTCS. Sponsored by UCB