The drug was proven to be efficacious and generally well tolerated in adults with newly diagnosed epilepsy.
Elinor Ben‐Menachem, MD, PhD
Results from 2 phase 3 trials of lacosamide demonstrate a similar efficacy, tolerability and safety profile compared to carbamazepine-CR as monotherapy in patients with newly diagnosed epilepsy.
Investigators reported safety results from the double-blind extension (SP0994; NCT01465997) of the large-scale noninferiority trial SP0993 (NCT01243177), as well as a post hoc analyses of pooled 12- and 24-month data on seizure freedom and treatment-emergent adverse events (TEAEs) from both trials.
The phase 3, randomized, double-blind, noninferiority trial included 886 patients who were randomly assigned 1:1 to either a starting target dose of 200 mg/d of lacosamide or 400 mg/d of carbamazepine-CR. Patients were assessed at 6 months and were escalated to a second target dose (lacosamide 400 mg/d; carbamazepine-CR 800 mg/d) if seizures continued. Those placed in a second target dose group restarted their 6-month evaluation when administered the new dosage.
Those who were seizure-free while completing the noninferiority trial were eligible for the phase 3 extension trial that assessed safety outcomes of lacosamide compared to carbamazepine-CR. The multicenter, double-blind, double-dummy extension trial conducted between May 2012 and January 2017 included 548 participants across 149 sites in 29 countries. Patients were assessed every 13 weeks and were allowed one dose reduction (lacosamide 100 mg/d or carbamazepine-CR 200 mg/d) for tolerability reasons. Those who experienced a seizure at the third target dose during the initial trial were excluded.
Of the 548 participants in the extension trial, 211 (75.6%) and 180 (66.9%) patients on lacosamide or carbamazepine-CR finished the trial, respectively. Among the 2 groups, 181 (64.9%) patients treated with lacosamide reported TEAEs compared to 182 (67.7%) patients who received carbamazepine-CR. Of the 211 patients who received lacosamide, 32 (11.5%) reported a serious TEAE, and 12 (4.3%) discontinued treatment due to TEAEs. In comparison, 22 (8.2%) patients on carbamazepine-CR reported a serious TEAE and 21 (7.8%) discontinued treatment due to TEAEs.
In the post-hoc analyses, estimated proportions of patients who were treated with lacosimide and had 12- and 24-month seizure freedom from first dose were 50.8% (95% CI, 46.2%-55.4%) and 47% (42.2%-51.7%), respectively, compared to 54.9% (50.3%-59.6%) and 50.9% (46.0%‐55.7%) of patients who received carbamazepine-CR.
Among the 886 patients treated in the combined trials, 245 (27.7%) had no comorbid conditions, 305 patients (34.4%) had 1 to 2 comorbid conditions, and 336 (37.9%) patients had 3 or more comorbid conditions. The most commonly experienced comorbidities were hypertension (lacosamide, 20.3%; carbamazepine‐CR, 24.2%) and hypercholesterolemia (lacosamide, 7.4%; carbamazepine‐CR, 9.7%). Notably, the incidence of TEAEs and discontinuation due to TEAEs was increased among those with a greater number of comorbidities.
Ben-Menachem E, Hans P, Kiyohito T, et al. Long-term safety and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy. Published online November 21, 2019. Epilepsia. doi:10.1111/epi.16381