title: 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: OBJECTIVE
  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.affiliation: Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. Electronic address: holger.lerche@uni-tuebingen.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.affiliation: Neurosciences, GlaxoSmithKline, 980 Great West Rd, Brentford, TW8 9GS, UK. Electronic address: jerzy.2.daniluk@gsk.com.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Daniluk
authors.affiliation: Neurosciences, GlaxoSmithKline Research and Development, 1-3 Iron Bridge Road, Uxbridge, UB11 1BT, UK. Electronic address: narinder.k.lotay@gsk.com.
authors.forename: Narinder
authors.initials: N
authors.lastname: Lotay
authors.affiliation: Neurosciences, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709, USA(3). Electronic address: sarah@derossett-uk.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: DeRossett
authors.affiliation: Clinical Statistics, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. Electronic address: suzanne.edwards@parexel.com.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Edwards
authors.affiliation: Bethel Epilepsy Centre, Mara Hospital, Maraweg 21, D-33617 Bielefeld, Germany. Electronic address: christian.brandt@mara.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Brandt
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077213:Lamotrigine; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D010655:Phenylenediamines / Q000008:administration & dosage* / Q000009:adverse effects; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage; D014635:Valproic Acid / Q000008:administration & dosage
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; D014227:Triazines; C101866:ezogabine; D002220:Carbamazepine; D000077287:Levetiracetam; D014635:Valproic Acid; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D010889:Piracetam
keywords: Adjunctive therapy; Anti-epileptic; Epilepsy