title: Efficacy and safety of Losigamone in partial seizures: a randomized double-blind study.
abstract: The objective of the study was to investigate the efficacy and safety of two different dosages of Losigamone (LSG) in add-on treatment of partial seizures. In a multi-center, double-blind, randomized clinical trial, patients received one of three 12-week treatments: placebo, LSG 1200 mg/day, or 1500 mg/day, in addition to up to three standard anticonvulsants after a prospective period of 12 weeks to assess baseline seizure frequency. The primary efficacy measure was the relative reduction of seizure frequency per 4 weeks in the double-blind phase as compared to baseline. In the intention-to-treat population of 264 patients, the relative median reduction of partial seizure frequency was 3.3% for placebo, 19.7% for LSG 1200 mg/day, and 25.3% for LSG 1500 mg/day. The differences of both LSG groups versus placebo were significant (P<0.01, two-tailed). In the responder analysis, 11.8% of the patients in the placebo group, 17.2% in the LSG 1200 mg/day group, and 29.3% in the LSG 1500 mg/day group showed a seizure reduction versus baseline of at least 50%. A positive association between dosage and response was observed (P=0.003). Adverse events during treatment were reported by 58.8% of the patients for placebo, by 62.1% for LSG 1200 mg/day and by 76.1% for LSG 1500 mg/day. Most events in the LSG groups occurred during the first 4 weeks of double-blind (during or immediately after up-titration) and subsided quickly. Over the last 4 weeks of treatment, the incidence of adverse events in the LSG groups was close to the placebo level. Based on the study's results, LSG is an effective and safe add-on drug for refractory partial epilepsy in adults.
authors.affiliation: Epilepsy Unit, INSERM 0224, CHU Pitié-Salpêtrière, 91, Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. magali.debacker@psl.ap-hop-paris.fr
authors.forename: M
authors.initials: M
authors.lastname: Baulac
authors.forename: S
authors.initials: S
authors.lastname: Klement
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D005663:Furans / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000032:analysis
chemical_list: D000927:Anticonvulsants; D005663:Furans; C065427:losigame; D005723:gamma-Glutamyltransferase