title: Conversion to lacosamide monotherapy in the treatment of focal epilepsy: results from a historical-controlled, multicenter, double-blind study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy.
  
  
  METHODS
  This historical-controlled, double-blind study (NCT00520741) enrolled patients aged 16-70 years on stable doses of 1-2 antiepileptic drugs (AEDs) and experiencing 2-40 partial-onset seizures per 28 days during the 8-week prospective Baseline. Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose. Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase. The primary assessment was the Kaplan-Meier-predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥ 1 predefined seizure-related exit criterion by day 112, compared with the historical-control threshold (65.3%).
  
  
  RESULTS
  Four hundred twenty-five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥ 1 exit criterion; the Kaplan-Meier-predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6-35.5%) was lower than the historical control. When exit events, withdrawal due to treatment-emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8-37.8%) was also lower than the historical control. Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%). Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to-moderate in intensity. Seventy-two patients (16.9%) discontinued due to TEAEs. Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs.
  
  
  CONCLUSIONS
  Lacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy.
authors.affiliation: Consultants in Epilepsy and Neurology, PLLC, Boise, Idaho, U.S.A.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Wechsler
authors.forename: George
authors.initials: G
authors.lastname: Li
authors.forename: Jacqueline
authors.initials: J
authors.lastname: French
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: O'Neill
authors.initials: O
authors.lastname: D'Cruz
authors.forename: Paulette
authors.initials: P
authors.lastname: Williams
authors.forename: Robin
authors.initials: R
authors.lastname: Goodson
authors.forename: Melissa
authors.initials: M
authors.lastname: Brock
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000592:standards; D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000592:standards; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000175:diagnosis; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide
keywords: Focal epilepsy; Historical control; Lacosamide; Monotherapy; Partial-onset seizures