Glycine antagonist (GV150526) in acute stroke: A multicentre, double-blindplacebo-controlled phase II trial

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including p ermanent middle cerebral artery occlusion in the rat. GV150526 was very wel l tolerated in early human studies. The purpose of this randomised, double- blind, multicentre, placebo-controlled trial was to assess the safety and p opulation pharmacokinetics of GV150526 in patients with a clinical diagnosi s of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loadi ng dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following obser vation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduce d mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment . The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores less than or equal to5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 1 5%). There was also an imbalance in the proportion of patients with haemorr hagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mort ality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/ 400 mg and GV 800 mg/200 mg groups, respecti vely (no significant difference). Similarly, adverse events, though consist ent with an acute stroke population, appeared more often in the GV 800 mg/2 00 mg group. Functional outcomes at 1 month also showed imbalances, the per centage of patients with a Barthel Index score of greater than or equal to 95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/ 400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a progn ostically significant baseline difference between the groups rather than th e effect of GV150526. GV150526 was generally well tolerated in patients wit h a clinical diagnosis of acute stroke and formal efficacy studies were con sidered justified. Copyright (C) 2001 S. Karger AG, Basel.