Safety and tolerability of arundic acid in acute ischemic stroke

L. Creed Pettigrew; Scott E. Kasner; Gregory W. Albers; Mark Gorman; James C. Grotta; David G. Sherman; Yosuke Funakoshi; Hideyasu Ishibashi

doi:10.1016/j.jns.2006.09.001

Safety and tolerability of arundic acid in acute ischemic stroke

L. Creed Pettigrew, Scott E. Kasner, Gregory W. Albers, Mark Gorman, James C. Grotta, David G. Sherman, Yosuke Funakoshi, Hideyasu Ishibashi

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	50-56
Number of pages	7
Journal	Journal of the Neurological Sciences
Volume	251
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jns.2006.09.001
State	Published - Dec 21 2006

Bibliographical note

Funding Information:
Financial support was provided by Ono Pharma USA Inc., Lawrenceville, NJ, as a grant awarded to each participating center and by NIH M01 RR02602 (University of Kentucky General Clinical Research Center). We thank Sherry Chandler Williams, E.L.S., for manuscript preparation and editing.

Funding

Financial support was provided by Ono Pharma USA Inc., Lawrenceville, NJ, as a grant awarded to each participating center and by NIH M01 RR02602 (University of Kentucky General Clinical Research Center). We thank Sherry Chandler Williams, E.L.S., for manuscript preparation and editing.

Funders	Funder number
Ono Pharma USA
University of Kentucky General Clinical Research Center
National Institutes of Health (NIH)
National Center for Research Resources	M01RR002602

Keywords

Arundic acid
Astrocytes
Ischemic
NIH Stroke Scale
Stroke

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1016/j.jns.2006.09.001

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title = "Safety and tolerability of arundic acid in acute ischemic stroke",

abstract = "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.",

keywords = "Arundic acid, Astrocytes, Ischemic, NIH Stroke Scale, Stroke",

author = "Pettigrew, {L. Creed} and Kasner, {Scott E.} and Albers, {Gregory W.} and Mark Gorman and Grotta, {James C.} and Sherman, {David G.} and Yosuke Funakoshi and Hideyasu Ishibashi",

note = "Funding Information: Financial support was provided by Ono Pharma USA Inc., Lawrenceville, NJ, as a grant awarded to each participating center and by NIH M01 RR02602 (University of Kentucky General Clinical Research Center). We thank Sherry Chandler Williams, E.L.S., for manuscript preparation and editing. ",

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AU - Pettigrew, L. Creed

AU - Kasner, Scott E.

AU - Albers, Gregory W.

AU - Gorman, Mark

AU - Grotta, James C.

AU - Sherman, David G.

AU - Funakoshi, Yosuke

AU - Ishibashi, Hideyasu

N1 - Funding Information: Financial support was provided by Ono Pharma USA Inc., Lawrenceville, NJ, as a grant awarded to each participating center and by NIH M01 RR02602 (University of Kentucky General Clinical Research Center). We thank Sherry Chandler Williams, E.L.S., for manuscript preparation and editing.

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N2 - 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.

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Safety and tolerability of arundic acid in acute ischemic stroke

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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