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

Publication ,  Journal Article
Grotta, J; Clark, W; Coull, B; Pettigrew, LC; Mackay, B; Goldstein, LB; Meissner, I; Murphy, D; LaRue, L
Published in: Stroke
April 1995

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 > or = 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.

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Published In

Stroke

DOI

ISSN

0039-2499

Publication Date

April 1995

Volume

26

Issue

4

Start / End Page

602 / 605

Location

United States

Related Subject Headings

  • Receptors, N-Methyl-D-Aspartate
  • Pipecolic Acids
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Injections, Intravenous
  • Humans
  • Female
  • Excitatory Amino Acid Antagonists
  • Double-Blind Method
 

Citation

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Grotta, J., Clark, W., Coull, B., Pettigrew, L. C., Mackay, B., Goldstein, L. B., … LaRue, L. (1995). Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial. Stroke, 26(4), 602–605. https://doi.org/10.1161/01.str.26.4.602
Grotta, J., W. Clark, B. Coull, L. C. Pettigrew, B. Mackay, L. B. Goldstein, I. Meissner, D. Murphy, and L. LaRue. “Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial.Stroke 26, no. 4 (April 1995): 602–5. https://doi.org/10.1161/01.str.26.4.602.
Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB, et al. Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial. Stroke. 1995 Apr;26(4):602–5.
Grotta, J., et al. “Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial.Stroke, vol. 26, no. 4, Apr. 1995, pp. 602–05. Pubmed, doi:10.1161/01.str.26.4.602.
Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB, Meissner I, Murphy D, LaRue L. Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial. Stroke. 1995 Apr;26(4):602–605.

Published In

Stroke

DOI

ISSN

0039-2499

Publication Date

April 1995

Volume

26

Issue

4

Start / End Page

602 / 605

Location

United States

Related Subject Headings

  • Receptors, N-Methyl-D-Aspartate
  • Pipecolic Acids
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Injections, Intravenous
  • Humans
  • Female
  • Excitatory Amino Acid Antagonists
  • Double-Blind Method