title: Evaluation of Eslicarbazepine acetate on cardiac repolarization in a thorough QT/QTc study.
abstract: This study investigated the effect of eslicarbazepine acetate (ESL) on cardiac repolarization in healthy adult volunteers. A randomized, placebo/active-controlled, 4-period crossover study was conducted in 67 participants. In 3 periods, participants received once-daily doses of ESL 1200 mg, ESL 2400 mg, and placebo for 5 days; in 1 period, participants received placebo on days 1 to 4 and a 400-mg moxifloxacin single dose on day 5. In each period, 24-hour 12-lead Holter monitoring was performed on days -;1 (baseline) and 5. There was no clinically relevant effect of ESL 1200 mg and 2400 mg versus placebo on cardiac depolarization or repolarization as measured by the QRS or QTc intervals, respectively. Mean PR interval increased following ESL 1200 mg and 2400 mg, but there was no participant with a PR interval above the upper limit of the normal range (200 ms). The upper bound of the 95% confidence interval for the placebo-corrected change from baseline of the individually corrected QT interval (QTcI) following administration of ESL 1200 mg and ESL 2400 mg was <10 ms at every time point. Moxifloxacin caused an increase in QTcI above the 10-ms threshold for clinical significance at several time points, demonstrating assay sensitivity. It is concluded that administration of ESL 1200 mg and ESL 2400 mg did not induce a clinically significant prolongation of the QTcI interval.
authors.affiliation: Department of Research and Development, BIAL-Portela & Co, S.A., S Mamede do Coronado, PortugalHealth Sciences Section, University of Aveiro, Aveiro, PortugalComprehensive PhaseOne, Miramar, FloridaERT-eResearchTechnology, Inc, Philadelphia, PennsylvaniaInstitute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vaz-Da-Silva
authors.forename: Teresa
authors.initials: T
authors.lastname: Nunes
authors.forename: Luis
authors.initials: L
authors.lastname: Almeida
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gutierrez
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Litwin
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-Da-Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory / Q000187:drug effects*; D005260:Female; D064368:Healthy Volunteers; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; C416835:eslicarbazepine acetate