Efficacy and safety of extended‐release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial‐onset seizures: a randomized controlled trial
| Autor: | E.I. Bogdanov, Waldemar Brola, Anna Czlonkowska, Vitalii Laskov, Anamarija Mrdjen, Urszula Fiszer, Maria Mazurkiewicz-Bełdzińska, Jacqueline French, David Burdette, Ildefonso Rodriguez-Leyva, Hrvoje Hecimovic |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent adjunctive therapy International Cooperation Population Oxcarbazepine Phases of clinical research partial-onset seizures Placebo Statistics Nonparametric law.invention Young Adult Drug Delivery Systems Double-Blind Method Randomized controlled trial law Internal medicine medicine Humans education Adverse effect Aged Retrospective Studies education.field_of_study Dose-Response Relationship Drug business.industry Original Articles refractory epilepsy General Medicine Middle Aged extended-release oxcarbazepine Carbamazepine Neurology Tolerability Concomitant Anesthesia Anticonvulsants Female Epilepsies Partial Neurology (clinical) business Follow-Up Studies medicine.drug |
| Zdroj: | Acta Neurologica Scandinavica |
| ISSN: | 1600-0404 0001-6314 |
| Popis: | TM ) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand 2014: 129: 143‐153. © 2013 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective – To evaluate the efficacy, tolerability, and safety of oncedaily 1200 mg and 2400 mg SPN-804 (Oxtellar XR TM , Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods – The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intentto-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results – Median percent reduction was -28.7% for placebo, 38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and 42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: 13.3%; 1200 mg: 34.5%, P = 0.02; 2400 mg: 52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug’s established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not associated with any new safety signals. Conclusions – Adjunctive once-daily SPN-804 improved seizure control in patients with inadequately controlled partial-onset seizures. Adverse event occurrence and discontinuations due to adverse events suggest improved tolerability vs previously published data with immediaterelease OXC. |
| Databáze: | OpenAIRE |
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