Efficacy and tolerability of adjunctive lacosamide in pediatric patients with focal seizures

Abstract

Objective: To evaluate efficacy and tolerability of adjunctive lacosamide in children and adolescents with uncontrolled focal (partial-onset) seizures.

Methods: In this double-blind trial (SP0969; NCT01921205), patients (age ≥4-<17 years) with uncontrolled focal seizures were randomized (1:1) to adjunctive lacosamide/placebo. After a 6-week titration, patients who reached the target dose range for their weight (<30 kg: 8-12 mg/kg/d oral solution; ≥30-<50 kg: 6-8 mg/kg/d oral solution; ≥50 kg: 300-400 mg/d tablets) entered a 10-week maintenance period. The primary outcome was change in focal seizure frequency per 28 days from baseline to maintenance.

Results: Three hundred forty-three patients were randomized; 306 (lacosamide 152 of 171 [88.9%]; placebo 154 of 172 [89.5%]) completed treatment (titration and maintenance). Adverse events (AEs) were the most common reasons for discontinuation during treatment (lacosamide 4.1%; placebo 5.8%). From baseline to maintenance, percent reduction in focal seizure frequency per 28 days for lacosamide (n = 170) vs placebo (n = 168) was 31.7% (p = 0.0003). During maintenance, median percent reduction in focal seizure frequency per 28 days was 51.7% for lacosamide and 21.7% for placebo. Fifty percent responder rates (≥50% reduction) were 52.9% and 33.3% (odds ratio 2.17, p = 0.0006). During treatment, treatment-emergent AEs were reported by 67.8% lacosamide-treated patients (placebo 58.1%), most commonly (≥10%) somnolence (14.0%, placebo 5.2%) and dizziness (10.5%, placebo 3.5%).

Conclusions: Adjunctive lacosamide was efficacious in reducing seizure frequency and generally well tolerated in patients (age ≥4-<17 years) with focal seizures.

Clinicaltrialsgov identifier: NCT01921205.

Classification of evidence: This trial provides Class I evidence that for children and adolescents with uncontrolled focal seizures, adjunctive lacosamide reduces seizure frequency.

Figure 1. SP0969 trial design

PBO = placebo. ^aThe highest possible dose per body weight category is shown for each taper period week. ^bPatients on lacosamide remained on their maintenance dose during the transition period, whereas patients in the placebo group initiated lacosamide in a double-blind fashion. On completion of the transition period, eligible patients entered the open-label extension on a weight-based dose (<30 kg: 10 mg/kg/d; ≥30–<50 kg: 6 mg/kg/d; ≥50 kg: 300 mg/d).

Figure 2. Patient disposition

FAS = full analysis set; PK-PPS = pharmacokinetic–per-protocol set; SS = safety set.

Figure 3. Analyses of focal seizure frequency per 28 days during maintenance

(A) Median percent reduction from baseline, (B) 50% responder rates, and (C) 75% responder rates, assessed for the overall population and for patients with and without concomitant sodium channel–blocking antiepileptic drugs (SCB AEDs). **p ≤ 0.01, ***p ≤ 0.001.