Abstract | BACKGROUND: Additional options are needed for monotherapy treatment of adults newly diagnosed with partial epilepsy. This trial compares the efficacy and tolerability of once-daily zonisamide with twice-daily controlled-release carbamazepine monotherapy for such patients. METHODS: In this phase 3, randomised, double-blind, parallel-group, non-inferiority trial, adults from 120 centres in Asia, Australia, and Europe, aged 18-75 years and newly diagnosed with partial epilepsy, were randomly assigned (in a 1:1 ratio, done with a computer-generated pseudorandom code) to receive zonisamide or carbamazepine. Patients, investigators, and sponsor personnel giving drugs, analysing outcomes, and interpreting data were masked to treatment allocation. After treatment initiation ( zonisamide 100 mg/day vs carbamazepine 200 mg/day [given in two doses]) and up-titration (to 300 mg/day vs 600 mg/day), patients entered a 26-78 weeks flexible-dosing period (200-500 mg/day vs 400-1200 mg/day, according to response and tolerance). Once patients were seizure-free for 26 weeks they entered a 26-week maintenance phase. The primary endpoint was the proportion of patients who achieved seizure freedom for 26 weeks or more in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT00477295. FINDINGS: 583 patients were randomly assigned to treatment groups (282 zonisamide, 301 carbamazepine), of whom 456 were analysed for the primary endpoint (per-protocol population: 223 zonisamide, 233 carbamazepine). 177 of 223 (79·4%) patients in the zonisamide group and 195 of 233 (83·7%) patients in the carbamazepine group were seizure-free for 26 weeks or more (adjusted absolute treatment difference -4·5%, 95% CI -12·2 to 3·1). The incidence of treatment-emergent adverse events was 170 (60%) in the zonisamide group versus 185 (62%) in the carbamazepine group, of which 15 (5%) versus 17 (6%) were serious and 31 (11%) versus 35 (12%) led to withdrawal. INTERPRETATION: FUNDING: Eisai Ltd.
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Authors | Michel Baulac, Martin J Brodie, Anna Patten, Joanna Segieth, Luigi Giorgi |
Journal | The Lancet. Neurology
(Lancet Neurol)
Vol. 11
Issue 7
Pg. 579-88
(Jul 2012)
ISSN: 1474-4465 [Electronic] England |
PMID | 22683226
(Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- Anticonvulsants
- Delayed-Action Preparations
- Isoxazoles
- Carbamazepine
- Zonisamide
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Topics |
- Adolescent
- Adult
- Aged
- Anticonvulsants
(administration & dosage, therapeutic use)
- Carbamazepine
(administration & dosage, therapeutic use)
- Delayed-Action Preparations
- Double-Blind Method
- Drug Administration Schedule
- Epilepsies, Partial
(diagnosis, drug therapy)
- Female
- Humans
- Isoxazoles
(administration & dosage, therapeutic use)
- Male
- Middle Aged
- Treatment Outcome
- Young Adult
- Zonisamide
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