(128) Long-term safety and efficacy of adjunctive lacosamide in the treatment of primary generalized tonic-clonic seizures: an open-label extension trial

Rationale: A double-blind, randomized, placebo-controlled trial (SP0982; NCT02408523) demonstrated efficacy and safety of lacosamide (LCM) as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures (PGTCS) in patients (≥4 years of age) with idiopathic generalized epilepsy (IGE). This ongoing open-label extension (OLE) (EP0012; NCT02408549) is assessing long-term safety, tolerability, and efficacy of adjunctive LCM in patients who completed SP0982 or failed randomization criteria at Baseline.

Methods: Patients who continued in the OLE transitioned in a double-blind fashion to age- and weight-based LCM dosing. During the OLE, doses could be adjusted in weekly steps ≤2 mg/kg/day or 100 mg/day to optimize tolerability and seizure control (min 4 mg/kg/day or 200 mg/day; max 12 mg/kg/day [pediatric patients < 50 kg], 600 mg/day [pediatric patients ≥50 kg], or 800 mg/day [adults ≥18 years]). At the time of this interim analysis (cut-off: 28 Aug 2019), the last SP0982 patients were enrolled in the OLE. Primary safety outcomes were treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, patients with increase in days with absence/myoclonic seizures, and incidences of new seizure types.

Results: Two hundred thirty-nine patients started the OLE (142 initiated LCM, 97 continued LCM) and received ≥1 LCM dose (safety set; mean age: 27.9 years; 56.1% female; median Baseline PGTCS frequency/28 days: 1.02). At the cut-off, 187 (78.2%) patients were ongoing and 52 (21.8%) had discontinued, most commonly due to withdrawn consent (7.5%), lack of efficacy (6.3%), and adverse events (4.6%). Median duration of LCM exposure was 595 days (range 20, 1416). 82.4% of patients had TEAEs (Table 1). Median percent change in PGTCS frequency/28 days from Combined Baseline of SP0982 (12 weeks Historical and 4 weeks Prospective) to Treatment period was −88.52% (range −100.0, 465.4) (n=238). 79.8% (190/238) of patients had ≥50% and 63.4% (151/238) had ≥75% reduction in PGTCS frequency/28 days; 6.3% (15/238) had ≥50% increase in PGTCS frequency. Among patients completing 22/46/94 weeks of treatment (n=207/176/107), 95 (45.9%), 55 (31.3%), and 29 (21.7%) were free from PGTCS, and 75 (36.2%), 44 (25.0%), and 20 (18.7%) were free from all generalized seizures, respectively. Few patients had an increase in number of days with absence/myoclonic seizures or incidence of new absence/myoclonic seizures (Table 2). Patients with absence seizures during Prospective Baseline (n=40) had a median percent reduction of −62.0% (range −100, 80) in number of days with absence seizures/28 days. Patients with myoclonic seizures during Prospective Baseline (n=41) had a median percent reduction of −85.4% (range −100, 286) in number of days with myoclonic seizures/28 days.

Conclusions: In this interim analysis, long-term LCM was well tolerated as adjunctive treatment for PGTCS in patients (≥4 years of age) with IGE. No new safety concerns were identified. Reductions in PGTCS frequency were observed and few patients had worsening of PGTCS, myoclonic, or absence seizures.

Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-sponsored