Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomised, placebo-controlled trial

• DOI: 10.1136/jnnp-2020-323524
• Publication Date: 2020-08-18T12:45:19Z
• Authors: David G Vossler; Susanne Knake; Terence J O'Brien; Masako Watanabe; Melissa Brock; Björn Steiniger-B...; Paulette Williams; Robert Roebling
• Keywords: Lacosamide; Adjunctive treatment

Objective To evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic epilepsy (IGE). Methods Phase 3, double-blind, randomised, placebo-controlled trial (SP0982; NCT02408523 ) IGE PGTCS taking 1–3 concomitant antiepileptic drugs. Primary outcome was time second during 24-week treatment. Results 242 were randomised received ≥1 dose medication (lacosamide/placebo: n=121/n=121). Patients (mean age: 27.7 years; 58.7% female) had a history generalised-onset (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). Median duration lacosamide/placebo 143/65 days. Risk developing significantly lower than placebo (Kaplan-Meier survival estimates 55.27%/33.37%; HR 0.540, 95% CI 0.377 0.774; p<0.001; n=118/n=121). could not be estimated (>50% did experience PGTCS) 77.0 days placebo. Kaplan-Meier freedom from at end the period (day 166) 31.3%/17.2% (difference 14.1%; p=0.011). More on ≥50% (68.1%/46.3%) ≥75% (57.1%/36.4%) reduction baseline frequency/28 days, observed (27.5%/13.2%) (n=119/n=121). 96/121 (79.3%) treatment-emergent adverse events (placebo 79/121 (65.3%)), most commonly dizziness (23.1%), somnolence (16.5%), headache (14.0%). No died trial. Conclusions Lacosamide efficacious generally safe IGE.