Abstracts

Rationale: A previously conducted Phase 2, multicenter, open-label pilot study (SP0961; NCT01118949) evaluated the safety of adjunctive lacosamide (LCM) in patients with idiopathic generalized epilepsy (IGE) and primary generalized tonic-clonic seizures (PGTCS). This open-label extension (OLE) study (SP0962; NCT01118962), following the initial trial, further assessed long-term safety of adjunctive LCM treatment in patients with PGTCS.Methods: Patients who completed SP0961 could enroll in SP0962. The initial LCM dose for each patient in SP0962 was the dose received at the end of SP0961 (300 or 400 mg/day). LCM dose in SP0962 could be increased (up to 800 mg/day) or decreased throughout the 56-week Treatment Phase to optimize tolerability and seizure control. New concomitant AEDs approved for PGTCS could be introduced, if needed. Primary variables were treatment-emergent adverse events (TEAEs) and withdrawals due to TEAEs. Other variables included percent change in PGTCS frequency/28 days from the SP0961 4-week Prospective Baseline or 16-week Combined Baseline (12-week Historical + 4-week Prospective), and change in number of days with absence or myoclonic seizures/28 days from 4-week Prospective Baseline. Long-term (6-month and 1-year) continuous freedom from PGTCS also was assessed.Results: In total, 39 of 40 patients who completed SP0961 enrolled in SP0962 (mean age 30.3 years, 71.8% female). Most (66.7%) were taking 2 3 concomitant AEDs at Baseline. All had a history of PGTCS; 66.7% and 53.8% had a history of absence and myoclonic seizures, respectively. A total of 29 (74.4%) completed the study. During the OLE, 82.1% of patients had >12 months of LCM exposure; the mean modal dose was 428.2 mg/day. Overall, 94.9% of patients reported 1 TEAE; 2 patients discontinued prematurely due to TEAEs (abnormal behavior and confusional state). One patient each experienced a TEAE of increased absence seizures and increased myoclonic seizures. The most frequently reported TEAEs (>15%) were dizziness (25.6%), upper respiratory tract infection (25.6%), headache (17.9%), and tremor (15.4%). During the Prospective Baseline, mean absence and myoclonic seizure days/28 days were 4.9 9.1 and 4.3 7.7, respectively; mean change in the Treatment Period was -2.4 5.5 days/28 days for absence and -2.8 6.4 days/28 days for myoclonic seizures. Median percent reduction in PGTCS frequency/28 days was 89.3% from Prospective Baseline to the Treatment Period and 72.3% from Combined Baseline to the Treatment Period. A total of 64.1% and 35.9% of patients were free from PGTCS for 6 months and 1 year, respectively. Conclusions: Tolerability results from this OLE were similar to those from the initial pilot study, and no major safety concerns arose after long-term treatment (>12 months) with adjunctive LCM in patients with IGE. LCM reduced PGTCS frequency in adults with IGE, and the frequency of absence and myoclonic seizures was generally unchanged or reduced. These results support further evaluation of LCM for the treatment of PGTCS in well-controlled studies. Funded by UCB Pharma