Internal medicine

Pathology

Pediatrics

Placebo

Epilepsy

Psychiatry

Randomized controlled trial

Alternative medicine

Lacosamide

Adjunctive treatment

Anesthesia

Medicine

Journal of Neurology Neurosurgery & Psychiatry

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

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