Safety and tolerability of the flutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke: Results of a phase IIa randomized trial

James Grotta, Wayne Clark, Bruce M Coull, L. Creed Pettigrew, Bruce Mackay, Larry B. Goldstein, Irene Meissner, Deborah Murphy, Linda LaRue

Research output: Contribution to journalArticle

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Abstract

Background and Purpose: CGS 19755 is a competitive N-methyl-D-aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. Methods: At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. Results: Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of ≥70 at the terminal visit. Conclusions: We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.

Original languageEnglish (US)
Pages (from-to)602-605
Number of pages4
JournalStroke
Volume26
Issue number4
StatePublished - Apr 1995
Externally publishedYes

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selfotel
Stroke
Safety
Placebos

Keywords

  • Cerebral ischemia
  • Glutamate antagonists
  • Glutamates
  • Neuroprotection

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Safety and tolerability of the flutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke : Results of a phase IIa randomized trial. / Grotta, James; Clark, Wayne; Coull, Bruce M; Pettigrew, L. Creed; Mackay, Bruce; Goldstein, Larry B.; Meissner, Irene; Murphy, Deborah; LaRue, Linda.

In: Stroke, Vol. 26, No. 4, 04.1995, p. 602-605.

Research output: Contribution to journalArticle

Grotta, J, Clark, W, Coull, BM, Pettigrew, LC, Mackay, B, Goldstein, LB, Meissner, I, Murphy, D & LaRue, L 1995, 'Safety and tolerability of the flutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke: Results of a phase IIa randomized trial', Stroke, vol. 26, no. 4, pp. 602-605.
Grotta, James ; Clark, Wayne ; Coull, Bruce M ; Pettigrew, L. Creed ; Mackay, Bruce ; Goldstein, Larry B. ; Meissner, Irene ; Murphy, Deborah ; LaRue, Linda. / Safety and tolerability of the flutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke : Results of a phase IIa randomized trial. In: Stroke. 1995 ; Vol. 26, No. 4. pp. 602-605.
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AU - Pettigrew, L. Creed

AU - Mackay, Bruce

AU - Goldstein, Larry B.

AU - Meissner, Irene

AU - Murphy, Deborah

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