Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures.

Abstract

PURPOSE:

To assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in combination with specified monotherapy antiepileptic drug (AED) treatments in adults with uncontrolled partial-onset seizures using a flexible dosing regimen.

METHODS:

NCT01227902 was an open-label, uncontrolled study of flexibly dosed EZG/RTG. Adults with partial-onset seizures must have been taking either carbamazepine/oxcarbazepine (CBZ/OXC), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). The study comprised a screening/baseline phase, a 4-week titration phase (initiation on 150mg/day [50mg three times daily (TID)] with weekly increases of 150mg/day [50mg TID] over 4 weeks to 600mg/day), and a flexible dose evaluation (FDE) phase (optional weekly dose changes of 50-150mg/day, to an optimal daily dosage [300-1200mg/day]). The primary efficacy endpoint was percentage of patients experiencing a ≥50% reduction from baseline in partial seizure frequency (responder rate) during the treatment phase (titration and FDE phases). Safety and tolerability were also assessed.

RESULTS:

Patients (N=203) were enrolled and received ≥1 dose of EZG/RTG. The dose of EZG/RTG prescribed most frequently during the treatment phase was 600mg/day for all AED groups. Responder rates during the treatment phase were: 40.0% (CBZ/OXC), 32.0% (LTG), 50.0% (LEV), and 56.9% (VPA). Treatment-emergent adverse events occurred in 82% (CBZ/OXC), 76% (LTG), 73% (LEV), and 67% (VPA) of patients; most were of mild-to-moderate intensity.

CONCLUSIONS:

EZG/RTG was effective as adjunctive therapy to CBZ/OXC, LTG, LEV, and VPA, using a flexible dosing regimen, in adults with partial-onset seizures; safety and tolerability were consistent with that previously observed.

• Authors: Holger Lerche, Jerzy Daniluk, Narinder Lotay, Sarah DeRossett, Suzanne Edwards, Christian Brandt
• Journal: Seizure (Seizure) Vol. 30 Pg. 93-100 (Aug 2015) ISSN: 1532-2688 [Electronic] England
• PMID: 26216692 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Anticonvulsants
• Carbamates
• Phenylenediamines
• Triazines
• ezogabine
• Carbamazepine
• Levetiracetam
• Valproic Acid
• Lamotrigine
• Oxcarbazepine
• Piracetam

Topics

• Aged
• Anticonvulsants (administration & dosage, adverse effects)
• Carbamates (administration & dosage, adverse effects)
• Carbamazepine (administration & dosage, analogs & derivatives)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Epilepsies, Partial (drug therapy, physiopathology)
• Female
• Humans
• Kaplan-Meier Estimate
• Lamotrigine
• Levetiracetam
• Male
• Middle Aged
• Oxcarbazepine
• Phenylenediamines (administration & dosage, adverse effects)
• Piracetam (administration & dosage, analogs & derivatives)
• Seizures (drug therapy, physiopathology)
• Treatment Outcome
• Triazines (administration & dosage)
• Valproic Acid (administration & dosage)