Long-Term Efficacy and Tolerability of Adjunctive Lacosamide for the Treatment of Primary Generalized Tonic-Clonic Seizures in Patients by Maximum Dose Used: Interim Post Hoc Analysis
Abstract number :
1.281
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825646
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Terence O'Brien, MD - Monash University & Department of Neurology, Alfred Health; David Vossler, MD – University of Washington & Valley Medical Center; Mark Kristof Farkas, MD – Semmelweis University; Svetlana Dimova, MD, PhD – UCB Pharma, Brussels; Bjoern Steiniger-Brach, PhD – UCB Pharma, Brussels; Carrie McClung, MS – UCB Pharma, Raleigh; Paulette Williams, MS – UCB Pharma, Raleigh; Robert Roebling, MD – UCB Pharma, Monheim am Rhein; Masako Watanabe, MD – Shinjuku Neuro Clinic & National Center of Neurology and Psychiatry
Rationale: A double-blind, randomized, placebo-controlled trial (SP0982/NCT02408523) demonstrated efficacy and safety of adjunctive lacosamide (LCM) for uncontrolled primary generalized tonic-clonic seizures (PGTCS) in patients (≥ 4 years) with idiopathic generalized epilepsy. The open-label extension trial (OLE; EP0012/NCT02408549) allowed LCM doses up to 800 mg/day (max. approved dose 400 mg/day). The objective of this post-hoc analysis was to evaluate the efficacy and tolerability of long-term adjunctive LCM for PGTCS by maximum dose used (per/above US label).
Methods: Patients were eligible for the OLE if they completed the double-blind trial/met trial exit criteria/discontinued early or were screen failures. During the OLE, LCM doses (age- and weight-based) could be adjusted to optimize tolerability/seizure control. This post-hoc interim analysis (cutoff: August 28, 2019) assessed outcomes from first visit in EP0012 in subgroups of patients by maximum LCM dose used, per US label (≤ 400 mg/day in adults and children weighing > 50kg, ≤ 8 mg/kg/day in children 30–50 kg, and ≤ 12 mg/kg/day in those 11–30 kg), or above-label.
Results: Of patients who received ≥ 1 LCM dose during the OLE (Safety Set [SS]), 180 received per-label doses only (mean age: 28.1 years; 53.3% female; mean epilepsy duration: 15.1 years; median Baseline PGTCS frequency/28 days: 1.0) and 58 had above-label doses (mean age: 27.3 years; 63.8% female; mean epilepsy duration: 15.4 years; median Baseline PGTCS frequency/28 days: 1.1). More patients with above-label doses initiated LCM treatment during the OLE (70.7% vs 56.1%). Mean/median/Q1/Q3 maximum LCM dose (mg/day) was 378/400/400/400 (per-label) and 565/500/500/600 (above-label) (mean exposure: 614.4 days [per-label]; 703.4 days [above-label]). At cutoff, 21.1% patients (per-label) and 24.1% (above-label) had discontinued LCM. In the per-label and above-label group, respectively, 81.6% and 75.9% patients had ≥ 50% reduction in PGTCS frequency/28 days from Baseline and 69.3% and 46.6% had ≥ 75% reduction; 5.0% and 10.3% had ≥ 50% increase in PGTCS frequency; response was sustained over time in both subgroups (Fig. 1; Full Analysis Set [FAS]). 38.0% patients (per-label) and 27.6% (above-label) were PGTCS-free for ≥ 1 year, with a longer duration of the ≥ 1-year PGTCS-free interval in the per-label subgroup (Fig. 2; FAS). Treatment-emergent adverse events (TEAEs), drug-related, serious, severe TEAEs, and discontinuations due to TEAEs occurred in 80.6%, 28.9%, 15.0%, 8.3%, and 3.9% patients (per-label) and 87.9%, 53.4%, 19.0%, 19.0%, and 5.2% patients (above-label), respectively (SS).
Conclusions: Long-term adjunctive LCM showed efficacy in PGTCS and was generally well-tolerated, independent of maximum LCM dose used (per/above US label). Patients with per-label doses had numerically higher efficacy responses and lower incidences of drug-related and severe TEAEs; discontinuations due to TEAEs were similar in the per/above-label subgroups.
Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded.
Anti-seizure Medications