Abstracts

Rationale: This non-inferiority trial (SP0993; NCT01243177) compared the efficacy and safety of lacosamide (LCM) vs carbamazepine controlled-release (CBZ-CR) as initial monotherapy in patients with newly diagnosed focal epilepsy. As antiepileptic treatment may be required before a precise diagnosis can be confirmed, patients with generalized tonic-clonic seizures (GTCS) without clear focal origin (distinction between primary and secondary GTCS could not be made) were also included. Results for the overall population and the subgroup of patients with GTCS are presented here. Methods: Patients aged ≥16 years with focal or GTCS (without evidence of focal onset) were randomized 1:1 to twice-daily LCM or CBZ-CR. Flexible up-titration to target dose (LCM 200/400/600mg/day; CBZ-CR 400/800/1200mg/day) was based on response to, and tolerability of the drug, reflecting clinical practice. Assessment of ‘pure’ efficacy was provided by Kaplan–Meier (KM)-predicted proportion of patients with 6-month seizure-freedom, following stabilization at the last evaluated dose. Patients completing 6 months’ treatment without a seizure, entered a 6-month maintenance period. Results: A total of 886 patients received trial medication (full analysis set [FAS]: LCM 444; CBZ-CR 442), of whom 805 had no important protocol deviations (per protocol set [PPS]: 408, 397). Patients had a mean (SD) age of 41.8 (17.6) years (range 16–87 years) and 53.6% were male. Overall (FAS), 530 patients (LCM 266/444 [59.9%]; CBZ-CR 264/442 [59.7%]) completed the trial. Treatment-emergent adverse events were reported by 328/444 (73.9%) patients on LCM and 332/442 (75.1%) on CBZ-CR, and were the most common reason for discontinuation (LCM 48 [10.8%]; CBZ-CR 69 [15.6%]). In the PPS for the overall population, 307/408 (75.2%) patients on LCM and 285/397 (71.8%) on CBZ-CR completed 6 months on last evaluated dose without seizure. KM-predicted proportion of patients with 6-month seizure-freedom was 91.5% with LCM vs 92.8% with CBZ-CR. LCM was non-inferior to CBZ-CR (treatment difference -1.3% [-5.3%, 2.7%]; Table 1). Results were similar in FAS. A history of GTCS only was reported for 40/444 (9.0%) patients in the LCM and 39/442 (8.8%) in the CBZ-CR groups. In the PPS for the GTCS subgroup, 26/36 (72.2%) patients on LCM and 26/35 (74.3%) on CBZ-CR completed 6 months without seizure. KM-predicted proportion of GTCS patients with 6-month seizure-freedom was 95.4% with LCM vs 96.7% with CBZ-CR (treatment difference -1.3% [-11.2%, 8.7%]; Table 1). Results were similar in FAS. Conclusions: LCM was non-inferior to CBZ-CR as assessed by 6-month seizure-freedom, and was well tolerated as monotherapy by patients with newly diagnosed epilepsy. Efficacy results for the GTCS subgroup were similar to those of the overall population, indicating that inclusion of patients with GTCS did not influence trial findings. Funding: UCB Pharma-sponsored.