Long-Term Safety and Tolerability of Eslicarbazepine Acetate as Add-On Treatment in Patients with Focal Seizures: Results from Four 1-Year Open-label Extension Phase III Studies
Abstract number :
V.075
Submission category :
7. Anti-seizure Medications / 7D. Drug Side Effects
Year :
2021
Submission ID :
1826211
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:53 AM
Authors :
Antonio Gil-Nagel, MD, PhD - Hospital Ruber International, Madrid, Spain; Guillermo Castilla Fernández – BIAL- Portela & Ca, S.A., S. Mamede do Coronado, Portugal; Miguel M. Fonseca – BIAL- Portela & Ca, S.A., S. Mamede do Coronado, Portugal; Fábio Ikedo – BIAL- Portela & Ca, S.A., S. Mamede do Coronado, Portugal; Ana Pereira – BIAL- Portela & Ca, S.A., S. Mamede do Coronado, Portugal; Joana Moreira – BIAL- Portela & Ca, S.A., S. Mamede do Coronado, Portugal; Helena Gama – BIAL- Portela & Ca, S.A., S. Mamede do Coronado, Portugal
Rationale: The long-term safety of antiseizure medications (ASMs) reflects their potential for chronic, cumulative dose effects; rare, but potentially serious late idiosyncratic effects and late, dose-related effects. Drug tolerability is also a significant factor in treatment maintenance and medication adherence1. We aim to evaluate the long-term (1-year exposure) safety and tolerability of eslicarbazepine acetate (ESL) as adjunctive therapy in patients with refractory focal seizures taking ASMs in four open-label extension (OLE) studies.
Methods: BIA-2093- 301, -302, -303 and -304 were Phase III, double-blind (DB), randomized, placebo-controlled studies that followed a similar design with once-daily ESL administered for 12 weeks (maintenance period). The differences in study designs were the number of ESL doses tested and the titration/tapering-off periods (BIA-2093- 301 and −302 had three ESL arms: 400 mg, 800 mg, 1200 mg; BIA-2093 −303 and −304 had two: 800 mg or 1200 mg). Patients completing DB studies were eligible to enter a 1-year OLE study following ESL administration. Safety and tolerability data from patients enrolled in the 1-year OLE studies were pooled and analysed.
Results: Safety population of the four 1-year OLE studies was composed by 1312 patients (301, n=314; 302, n=325; 303, n=194; 304, n=479). Of the 1312 patients enrolled, 958 (73.0%) completed the OLE studies. Treatment emergent adverse events (TEAEs) were reported by 68.8% (n=903) of patients during OLE studies. Most frequently TEAEs were: dizziness (18.2%; n=239); headache (12%; n= 158); somnolence (8.5%; n=111); nausea (5.5%; n= 72); nasopharyngitis (4.6%;n=60), vomiting (4.6%; n=60) and diplopia (4.4%; n=58).
Related TEAEs were reported in 47.8% (n=627) of patients. Most frequent related TEAEs were dizziness (15.3%; n=201), somnolence (7.5%; n=99), diplopia (6.3%; n=83), headache (4.2%; n= 55) and nausea (4.0%; n=53). Serious related TEAEs were found in 3.0% (n=40) of patients. Most frequent serious related TEAEs were drug toxicity (0.2%; n=2), partial seizures (0.2%; n=2) and suicide attempt (0.2%; n=2). Fifty-nine (4.5%) patients discontinued due to related TEAEs. Most frequent related TEAEs that led to discontinuation were dizziness (0.8%; n=11), vomiting (0.2%; n=3), ataxia (0.2%; n=2), and suicide attempt (0.2%; n=2). Two patients (0.2%) presented related TEAE that led to death: one patient with severe coronary atherosclerosis and sudden death, and another with status epilepticus. References: 1- Gaitattzis A, Sander JW. The Long-Term safety of antiepileptic drugs. CNS Drugs (2013) 27:435-455
Conclusions: Long-term treatment with add-on ESL was generally well tolerated and demonstrated a safety profile consistent with short term-controlled studies in patients with focal seizures over the 1-year four OLE studies with no new safety concerns arising with long term ESL treatment.
Funding: Please list any funding that was received in support of this abstract.: BIAL- Portela & Ca, S.A., S. Mamede do Coronado, Portugal.
Anti-seizure Medications