Conversion to lacosamide monotherapy in the treatment of focal epilepsy: Results from a historical‐controlled, multicenter, double‐blind study

Summary 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. Significance Lacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.