Abstracts

Rationale:
To compare long-term safety of adjunctive lacosamide (LCM) in pediatric (peds) and adult patients with PGTCS to patients with focal (partial)-onset seizures.
Method:
PGTCS peds (≥4 to ≤17 years) and adult (≥18 years) pools included interim data (cut-off: 28Aug19) from patients with PGTCS and idiopathic generalized epilepsy taking LCM (4–12mg/kg/day syrup/200–800mg/day tablets) in double-blind (DB) (SP0982: NCT02408523) and open-label extension (OLE) trials (EP0012: NCT02408549). The focal peds pool (≥4 to < 16 years) included interim data (cut-off: 01Nov16) from patients with focal seizures taking LCM (2–12mg/kg/day syrup/100–600mg/day tablets) in open-label trials (SP0847: NCT00938431, SP848: NCT00938912, EP0034: NCT01964560). The focal adult pool (≥16 years) included data from patients with focal seizures taking 100–800mg/day LCM in DB (SP0667, SP0754: NCT00136019, SP0755: NCT00220415) and OLE trials (SP0615: NCT00552305, SP0756: NCT00522275, SP774: NCT00515619).
Results:
In PGTCS peds (N=55), focal peds (N=408), PGTCS adult (N=209), and focal adult (N=1327) pools, mean durations of LCM exposure were 624.5, 343.0, 652.9, and 907.6 days respectively. Median modal daily LCM doses were 8mg/kg/day in PGTCS and focal peds, and 400mg/day in PGTCS and focal adults. Most common concomitant antiepileptic drugs (≥25% of patients) were valproate, levetiracetam (LEV) and lamotrigine (LTG) in PGTCS peds, focal peds and PGTCS adults, and carbamazepine, LTG and LEV in focal adults (Table 1). The most common reasons for LCM discontinuation (≥7% of patients) were adverse events (AEs) and consent withdrawn in PGTCS peds and adults, lack of efficacy in focal peds, and lack of efficacy, AEs and consent withdrawn in focal adults. Treatment-emergent AEs (TEAEs) in ≥1.5 patients/100-person months were nasopharyngitis and somnolence in PGTCS peds; nasopharyngitis, vomiting, dizziness, headache and pyrexia in focal peds; headache and dizziness in PGTCS adults; and dizziness in focal adults (Table 2). TEAEs were considered to be drug-related in 38.2%, 36.8%, 54.5% and 76.9% patients in PGTCS peds, focal peds, PGTCS adult and focal adult pools, respectively. In peds, the most common drug-related TEAEs (≥8% of patients) were dizziness (18.2%), somnolence (14.5%) and nausea (10.9%) in the PGTCS pool, and dizziness (9.6%) and somnolence (8.6%) in the focal pool. In adults, the most common drug-related TEAEs (≥12% of patients) were dizziness (20.6%) and somnolence (12.9%) in the PGTCS pool, and dizziness (42.4%) and diplopia (17.6%) in the focal pool. No patients died in the PGTCS pools, 1 (0.2%) died in the focal peds pool (not considered drug-related) and 11 (0.8%) died in the focal adult pool (considered not/unlikely drug-related).
Conclusion:
Pooled analyses indicate long-term treatment with adjunctive LCM was generally well tolerated in peds and adults with PGTCS. Safety observations in patients with PGTCS were generally consistent with the known safety profile of LCM in patients with focal seizures.
Funding:
:UCB Pharma-sponsored