title: Long-term safety and efficacy in patients with uncontrolled partial-onset seizures treated with adjunctive lacosamide: results from a Phase III open-label extension trial.
abstract: OBJECTIVE
  To evaluate the long-term (up to 5 years exposure) safety and efficacy of lacosamide as adjunctive therapy in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs) in open-label extension trial SP756 (NCT00522275).
  
  
  METHODS
  Patients who completed the double-blind trial SP754 (NCT00136019) were eligible to participate in this open-label extension trial (SP756). At the conclusion of trial SP754, patients had transitioned to lacosamide 200 mg/day. Subsequent dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure reduction. Treatment-emergent adverse events (TEAEs), vital signs, body weight, clinical laboratory data, electrocardiography studies, and seizure frequency were evaluated.
  
  
  RESULTS
  A total of 308 patients received open-label lacosamide and 138 patients (44.8%) completed the long-term trial. The median modal dose (defined as the daily lacosamide dose a patient received for the longest duration during the treatment period) was 500 mg/day. The percentages of patients with lacosamide exposure >1, >2, >3, or >4 years were 75%, 63%, 54%, and 29%, respectively. Primary reasons for discontinuation were lack of efficacy (26%) and adverse events (11%). Common TEAEs (≥15%) were dizziness, headache, contusion, nausea, convulsion, nasopharyngitis, fall, vomiting, and diplopia. TEAEs that led to discontinuation in ≥1.0% of patients were dizziness (1.6%) and convulsion (1.0%). The median percent reductions from baseline of trial SP754 in 28-day seizure frequency were 53.4%, 55.2%, 58.1%, and 62.5%, respectively, for 1-, 2-, 3-, and 4-year completers. The ≥50% responder rates were 52.8%, 56.5%, 58.7%, and 62.5% for 1-, 2-, 3-, and 4-year completers, respectively. Seven of eight patients on lacosamide monotherapy for ≥12 months were deemed 50% responders. Of patients exposed to lacosamide ≥2 years, 3.1% remained seizure-free for a period ≥2 years.
  
  
  CONCLUSIONS
  Long-term (up to 5 years) lacosamide treatment was generally well tolerated. The safety profile of lacosamide observed in this trial is consistent with that established in previous double-blind, placebo-controlled trials. Although the open-label trial design limits the analysis of efficacy, long-term reduction in seizure frequency and maintenance of efficacy was observed.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. aatif.husain@duke.edu
authors.forename: Aatif
authors.initials: A
authors.lastname: Husain
authors.forename: Steve
authors.initials: S
authors.lastname: Chung
authors.forename: Edward
authors.initials: E
authors.lastname: Faught
authors.forename: Jouko
authors.initials: J
authors.lastname: Isojarvi
authors.forename: Cindy
authors.initials: C
authors.lastname: McShea
authors.forename: Pamela
authors.initials: P
authors.lastname: Doty
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects*; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects*; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods*; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D013995:Time; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide