Abstracts

Rationale: To evaluate efficacy and tolerability of adjunctive lacosamide (LCM) in children and adolescents with uncontrolled focal (partial-onset) seizures. Methods: In this double-blind, placebo-controlled trial (SP0969; NCT01921205), patients (≥4 to < 17 years) with uncontrolled focal seizures (≥2 seizures/28 days during 8 weeks pre-Baseline [BL]; ≥2 seizures during 8-week prospective BL) on a stable regimen of 1-3 antiepileptic drugs, were randomized (1:1) to LCM or placebo (PBO). Following 6-week flexible-Titration, those who reached the target dose-range for their body weight ( < 30kg: 8-12mg/kg/day syrup; ≥30 to < 50kg: 6-8mg/kg/day syrup; ≥50kg: 300-400mg/day tablets) entered 10-week Maintenance. The primary outcome was change in focal seizure-frequency/28 days from BL to Maintenance. 50% and 75% responder rates (patients with ≥50%/≥75% reduction from BL in focal seizure-frequency/28 days) were also assessed. Results: 343 patients received trial medication (LCM/PBO: 171/172) (Table 1), of whom 306 (LCM/PBO: 152 [88.9%]/154 [89.5%]) completed the Treatment period (Titration & Maintenance). 302 patients (LCM/PBO: 151 [88.3%]/151 [87.8%]) completed the trial and 299 (LCM/PBO: 151 [88.3%]/148 [86.0%]) planned to continue to the open-label extension. The most common reason for discontinuation was adverse events (AEs) (LCM/PBO: 7 [4.1%]/12 [7.0%]). Median BL focal seizure frequency/28 days was 10.41 for LCM and 8.77 for PBO. From BL to Maintenance, percent reduction for LCM (n=170) vs PBO (n=168) in focal seizure-frequency/28 days was 31.7% (p=0.0003). From BL to Treatment, percent reduction for LCM (n=170) vs PBO (n=169) was 30.2% (p < 0.0001) with similar percent reductions observed for LCM vs PBO in simple partial (focal aware) (30.8%), complex partial (focal with impaired awareness) (32.4%) and secondarily generalized (focal to bilateral tonic-clonic) (23.35%) seizures. Median percent reduction in focal seizure-frequency/28 days from BL to Maintenance was 51.7% for LCM and 21.7% for PBO (BL to Treatment: 45.6% for LCM; 16.4% for PBO). Responder rates from BL to Maintenance were higher with LCM vs PBO: 50% responders, 52.9% (90/170) vs 33.3% (56/168) (odds ratio [OR] 2.17; p=0.0006); 75% responders, 31.2% (53/170) vs 16.1% (27/168) (OR 2.25; p=0.0027). Responder rates from BL to Treatment were also higher with LCM vs PBO: 50% responders, 44.1% (75/170) vs 29.6% (50/169) (OR 1.81; p=0.0101); 75% responders, 23.5% (40/170) vs 8.9% (15/169) (OR 2.90; p=0.0009). 116/171 (67.8%) patients on LCM and 100/172 (58.1%) on PBO reported at least one TEAE during the Treatment period (Table 2); most had TEAEs that were mild or moderate in intensity. Somnolence and dizziness were the most common treatment-emergent AEs (TEAEs) with LCM during the Treatment period, and had higher incidences during Titration than Maintenance. During Treatment, psychiatric TEAEs were reported by 11 (6.4%) patients on LCM vs 11 (6.4%) on PBO. Conclusions: In children and adolescents (≥4 to < 17 years) with uncontrolled focal seizures, adjunctive LCM was effective in reducing seizure-frequency and generally well tolerated, with a favorable tolerability profile similar to that observed in adults. Funding: UCB Pharma-sponsored.