Abstract | OBJECTIVE: 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:
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Authors | Robert T Wechsler, George Li, Jacqueline French, Terence J O'Brien, O'Neill D'Cruz, Paulette Williams, Robin Goodson, Melissa Brock, ALEX-MT Study Group |
Journal | Epilepsia
(Epilepsia)
Vol. 55
Issue 7
Pg. 1088-98
(Jul 2014)
ISSN: 1528-1167 [Electronic] United States |
PMID | 24915838
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Wiley Periodicals, Inc. © 2014 International League Against Epilepsy. |
Chemical References |
- Acetamides
- Anticonvulsants
- Lacosamide
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Topics |
- Acetamides
(administration & dosage, adverse effects, standards)
- Adolescent
- Adult
- Aged
- Anticonvulsants
(administration & dosage, adverse effects, standards)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Administration Schedule
- Epilepsies, Partial
(diagnosis, drug therapy, physiopathology)
- Female
- Headache
(chemically induced, diagnosis)
- Humans
- Lacosamide
- Male
- Middle Aged
- Nausea
(chemically induced, diagnosis)
- Prospective Studies
- Treatment Outcome
- Young Adult
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