PMID- 17095018
OWN - NLM
STAT- MEDLINE
DCOM- 20070222
LR  - 20131121
IS  - 0022-510X (Print)
IS  - 0022-510X (Linking)
VI  - 251
IP  - 1-2
DP  - 2006 Dec 21
TI  - Safety and tolerability of arundic acid in acute ischemic stroke.
PG  - 50-6
AB  - 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.
FAU - Pettigrew, L Creed
AU  - Pettigrew LC
AD  - Stroke Program, Sanders-Brown Center on Aging, and Department of Neurology, 101 
      Sanders-Brown Building, University of Kentucky Medical Center, Lexington, KY 
      40536-0230, USA. cpetti@uky.edu
FAU - Kasner, Scott E
AU  - Kasner SE
FAU - Albers, Gregory W
AU  - Albers GW
FAU - Gorman, Mark
AU  - Gorman M
FAU - Grotta, James C
AU  - Grotta JC
FAU - Sherman, David G
AU  - Sherman DG
FAU - Funakoshi, Yosuke
AU  - Funakoshi Y
FAU - Ishibashi, Hideyasu
AU  - Ishibashi H
CN  - Arundic Acid (ONO-2506) Stroke Study Group
LA  - eng
GR  - M01 RR02602/RR/NCRR NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061107
PL  - Netherlands
TA  - J Neurol Sci
JT  - Journal of the neurological sciences
JID - 0375403
RN  - 0 (Caprylates)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (ONO2506)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Caprylates/adverse effects/*therapeutic use
MH  - Demography
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - *Drug Tolerance
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Ischemic Attack, Transient/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neuroprotective Agents/adverse effects/*therapeutic use
MH  - Severity of Illness Index
MH  - Survival Analysis
EDAT- 2006/11/11 09:00
MHDA- 2007/02/23 09:00
CRDT- 2006/11/11 09:00
PHST- 2006/05/19 00:00 [received]
PHST- 2006/08/30 00:00 [revised]
PHST- 2006/09/06 00:00 [accepted]
PHST- 2006/11/11 09:00 [pubmed]
PHST- 2007/02/23 09:00 [medline]
PHST- 2006/11/11 09:00 [entrez]
AID - S0022-510X(06)00375-3 [pii]
AID - 10.1016/j.jns.2006.09.001 [doi]
PST - ppublish
SO  - J Neurol Sci. 2006 Dec 21;251(1-2):50-6. doi: 10.1016/j.jns.2006.09.001. Epub 
      2006 Nov 7.