Abstracts

Rationale:
In an open-label pilot and extension study, adjunctive lacosamide (LCM) was well tolerated in patients (16–65 years) with idiopathic generalized epilepsy (IGE) and uncontrolled primary generalized tonic-clonic seizures (PGTCS) (Wechsler RT, et al. Epilepsy Res 2017;130:13-20). This double-blind trial evaluated efficacy and tolerability of LCM as adjunctive treatment for uncontrolled PGTCS in patients (≥4 years) with IGE.
Method:
Phase 3, double-blind, randomized, placebo (PBO)-controlled trial (SP0982; NCT02408523) of adjunctive LCM (up to 12 mg/kg/day or 400 mg/day) in patients (≥4 years) with IGE and uncontrolled PGTCS taking 1–3 concomitant antiepileptic drugs (AEDs). The primary outcome was time to second PGTCS during 24-week treatment; the key secondary outcome was freedom from PGTCS (estimated using Kaplan-Meier analysis) during 24-week treatment. We present subgroup analyses (prespecified and post hoc) of efficacy outcomes by age group (pediatric: < 18 years; adult: ≥18 years), baseline PGTCS frequency (≤2, >2 per 28 days), number of concomitant AEDs (1, 2, ≥3) at trial entry, number of lifetime AEDs (1, 2, ≥3), and use of sodium channel blocking AEDs, valproate, or levetiracetam at trial entry. Results242 patients were randomized and received ≥1 trial dose (LCM/PBO: n=121/n=121). All patients (mean age: 27.7 years; 58.7% female) had a history of generalized-onset seizures (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). 103 (85.1%) patients on LCM and 110 (90.9%) on PBO completed the trial; 18 (14.9%) on LCM and 11 (9.1%) on PBO discontinued, most commonly due to adverse events (8.3%/3.3%). The median treatment duration with LCM/PBO was 143/65 days. The risk of developing a second PGTCS during 24-week treatment was lower in patients on LCM than PBO overall and in all subgroups (Table). The median time to second PGTCS was not estimable for LCM ( >50% of patients did not experience a second PGTCS) and was 77.0 days for PBO. Kaplan-Meier estimated freedom from PGTCS at the end of treatment for LCM/PBO was 31.3%/17.2% (difference 14.1%; p=0.011) overall, 20.0%/12.0% in pediatric patients (n=24/25), 33.8%/18.8% in adult patients (n=94/96), 31.8%/20.4% in patients with ≤2 PGTCS per 28 days at Baseline (n=93/95), and 30.0%/4.9% in patients with >2 PGTCS per 28 days at Baseline (n=25/26). More patients on LCM than PBO had a ≥50% (68.1%/46.3%) or ≥75% (57.1%/36.4%) reduction from Baseline in PGTCS frequency/28 days (n=119/n=121), or had observed freedom from PGTCS during treatment (27.5%/13.2%) (n=109/n=114). Similar trends were seen in all analyzed subgroups (Figure). 96/121 (79.3%) patients on LCM and 79/121 (65.3%) on PBO had treatment-emergent adverse events (TEAEs). The most common TEAEs with LCM (≥10% of patients) vs PBO were dizziness (23.1% vs 5.8%), somnolence (16.5% vs 14.0%), and headache (14.0% vs 9.9%).
Conclusion:
LCM was efficacious and generally well-tolerated as adjunctive treatment for uncontrolled PGTCS in patients with IGE. Efficacy findings in all subgroups were consistent with the overall population.
Funding:
:UCB Pharma-sponsored