Rufinamide:: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy

被引:126
作者
Pålhagen, S
Canger, R
Henriksen, O
van Parys, JA
Rivière, ME
Karolchyk, MA
机构
[1] Novartis Pharma AG, CRD, CH-4002 Basel, Switzerland
[2] Linkoping Univ Hosp, Dept Neurol, SE-58185 Linkoping, Sweden
[3] Osped S Paolo, Ctr Epilessia, Milan, Italy
[4] Natl Ctr Epilepsy, N-1337 Sandvika, Norway
[5] Inst Epilepsie Bestrijding, Heemstede, Netherlands
关键词
AED; antiepileptic agents; rufinamide; seizures; pharmacokinetics;
D O I
10.1016/S0920-1211(00)00185-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. Methods: Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures were enrolled in this 28-day double-blind, placebo-controlled, weekly rising dose (400-1600 mg/day) trial. PK profiles were obtained after administration of single-dose rufinamide prior to and after the Double-blind phase. Results: In the evaluable patient population, seizure frequency decreased by 41% in the rufinamide group and increased by 52% in the placebo group (P = 0.040). Thirty-nine percent (39%) of rufinamide-treated and 16% of placebo-treated patients experienced reduction in seizure frequency of at least 50% relative to baseline (P = 0.096). Safety: Treatment-emergent adverse events (AEs) consisted mainly of neurologic signs and symptoms commonly associated with antiepileptic drugs (AEDs). Pharmacokinetics: At steady state, rufinamide reached a peak plasma concentration with a mean time (T-max) of 3.4 h and a mean half-life (t(1/2)) of 7.3 h. No autoinduction of rufinamide metabolism occurred. Rufinamide did not influence the plasma concentration of carbamazepine, phenytoin or valproate when added to these single AED regimens. Conclusion: Rufinamide has been shown, in this proof of principle trial, to be safe and effective in reducing seizure frequency in epileptic patients with no relevant influence on the metabolism of other AEDs. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:115 / 124
页数:10
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