Adjunctive lacosamide for focal epilepsy: an open-label trial evaluating the impact of flexible titration and dosing on safety and seizure outcomes

Epileptic Disord. 2017 Jun 1;19(2):186-194. doi: 10.1684/epd.2017.0907.

Abstract

To evaluate the safety and effectiveness of lacosamide in a real-life setting with the use of a flexible dose titration schedule and individualised maintenance doses up to the maximum approved dose of 400 mg/day. Adults with a diagnosis of focal seizures, with or without secondary generalization, were enrolled in this open-label Phase IV trial (NCT01235403). Lacosamide was initiated at 100 mg/day (50 mg bid) and uptitrated over a 12-week period to 200, 300 or 400 mg/day, based on safety and seizure control. Although dose increases were to be in increments of 100 mg/day, intermediate doses were permitted at each escalation step for one week for patients known to be particularly sensitive to starting new AEDs. After receiving a stable, effective dose for three weeks, patients entered the 12-week maintenance period. Primary outcomes were incidence of treatment-emergent adverse events (TEAEs) and withdrawal due to TEAEs. Seizure outcomes, all secondary, were median focal seizure frequency, ≥50% reduction in focal seizure frequency, and seizure freedom. One hundred patients with a mean age of 44 years were enrolled and 74 completed the trial. The incidence of TEAEs was 64.0% (n=100), with the most frequently reported (≥5% of patients) being dizziness, headache, and asthenia. Fourteen patients withdrew due to TEAEs, most frequently due to dizziness (six patients; 6.0%), vomiting (two patients; 2%), and tremor (two patients; 2%). Among patients with baseline and maintenance phase seizure data (n=75), median reduction in focal seizure frequency from baseline was 69.7% and the ≥50% responder rate was 69.3%. Among 74 patients who completed the maintenance phase, 21 (28.4%) were seizure-free. Flexible lacosamide dosing in this open-label trial was associated with a favourable tolerability and safety profile; the nature of the TEAEs was consistent with that observed in previous pivotal trials. Treatment with lacosamide was also associated with effective seizure control.

Keywords: a ;tiepileptic; dizziness; flexible dose; focal; individualised; seizure; titration.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / adverse effects
  • Acetamides / pharmacology*
  • Adult
  • Aged
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacology*
  • Drug Administration Schedule
  • Epilepsies, Partial / drug therapy*
  • Female
  • Humans
  • Lacosamide
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Young Adult

Substances

  • Acetamides
  • Anticonvulsants
  • Lacosamide

Associated data

  • ClinicalTrials.gov/NCT01235403