Safety and tolerability of arundic acid in acute ischemic stroke
- 作者：L. Creed Pettigrew ; Scott E. Kasner ; Gregory W. Albers ; Mark Gorman ; James C. Grotta ; David G. Sherman ; Yosuke Funakoshi ; Hideyasu Ishibashi
- 关键词：Arundic acid ; NIH Stroke Scale ; Stroke ; Ischemic ; Astrocytes
- 刊名：Journal of the Neurological Sciences
- 出版年：2006
- 期刊代码：178_0022510x
- 类别：med
- 出版时间：21 December 2006
- 卷：251
- 期：1-2
- 页码：50-56
- 文件大小：128 K
摘要
Arundic acid (AA; ONO-2506), a novel modulator of astrocyte activation, may improve neuronal survival after stroke. We conducted a multicenter, dose-escalating, randomized, double-blind Phase I trial of AA in acute ischemic stroke. Subjects were randomized to treatment with AA or placebo in sequential dose tiers of 2–12 mg/kg/h (10–16 patients/group) within 24 h of stroke onset. Study drug was infused for 1 h daily over 7 days, and follow-up terminated at 40 days. Neurological and functional outcomes were evaluated through Day 40 as exploratory endpoints. A total of 92 subjects were enrolled with no dose-related pattern of serious adverse events (AEs). Premature terminations caused by AEs occurred in four (8.2%) patients treated with AA and five (11.6%) treated with placebo. Two subjects treated with AA (4.1%) and four given placebo (9.3%) died. Exploratory efficacy analysis showed a trend toward improvement in the change from baseline National Institutes of Health Stroke Scale (NIHSS) in the 8 mg/kg/h AA group on Days 3 (p = 0.023 vs. placebo), 7 (p = 0.002), 10 (p = 0.003), and 40 (p = 0.018). A dose of 8 mg/kg/h AA produced a favorable trend in reduction of NIHSS that should be confirmed in a future clinical trial.