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Citation: JNS Volume 187, Supplement 1, page S255, June 2001

M. Bozik¹, M. Hommel⁵, J. Grotta², M. Fisher³, P. Fayad⁴, J. Bogousslavsky⁶, R. Brunell¹, L. Fernandes¹, S. Colby¹, T. Noonan¹, A. Douglass<sup>1

1</sup>Bristol-Myers Squibb; ²University of Texas Medical Center; ³University of Masscheusetts Memorial Healthcare; ⁴Yale University School of Medicine, USA
⁵Hospital de la Tronche, France
⁶Centre Hospitalier Universitaire Vaudois, Switzerland

Background: The novel fluoro-oxindole MaxiPost^TM is a potent and effective Ca2+ sensitive opener of maxi-K channels, which hyperpolarize neurons, reduce Ca2+ entry and decrease release of glutamate when open. We hypothesized that MaxiPost^TM may enhance neuronal tolerance to ischemia and improve clinical outcomes by augmenting this endogenous mechanism for regulating Ca2+ entry and membrane potential during stroke.
Objective: To determine the efficacy and safety of MaxiPost^TM 0.1 mg and 1.0 mg vs placebo in patients with signs and symptoms of acute ischemic stroke.
Methods: Approximately 1978 patients were enrolled at 200 worldwide sites between August, 1998 and November, 2000 in a randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of MaxiPost^TM 0.1 mg and 1.0 mg vs placebo. Patients ³ 18 years with signs and symptoms of acute ischemic cortical stroke, a historical Modified Rankin Scale score < 1, a baseline NIH Stroke Scale score 6­20 and baseline Modified Rankin Scale score ³ 2, who were eligible to receive the 1st dose of study drug within 6 hours of stroke symptom onset, were randomized to either MaxiPost^TM or placebo. Four doses, each administered as a 20-sec IV push, were given over 72 hr at approximately 24-hr intervals. Evaluations were completed during Days 1­5 and at Weeks 2 and 12. The primary outcome measure was change from baseline to Week 12 on the NIH Stroke Scale.
Secondary outcome measures at week 12 included: response on the Modified Rankin Scale, Modified Rankin (full scale) score, and response on the Barthel Index. Safety data included: adverse events, physical examination findings, vital signs, laboratory data, ECGs, and mortality rates. An independent Data Safety Monitoring Board reviewed safety data at prespecified intervals throughout the study.
Results and Conclusions: Patient enrollment was completed in November, 2000. Final efficacy results and key safety findings will be presented.