title: The BRAINS study: safety, tolerability, and dose-finding of repinotan in acute stroke.
abstract: OBJECTIVE
  Repinotan is a potent, serotonin (5-HT1A) full receptor agonist that interferes with ischemia-mediated neuronal cell death in animal models. This double-blind, placebo-controlled phase II study examined the safety, tolerability, and dose of repinotan in patients with acute ischemic stroke.
  
  
  METHODS
  Patients with acute hemispheric ischemia and a National Institutes of Health Stroke Scale of 4 to 25 were randomized to placebo or repinotan 0.5, 1.25, or 2.5 mg/day (d) given by continuous intravenous infusion for 72 hours. Treatment was started within six hours of symptom onset. Evaluations were performed at four weeks and three months.
  
  
  RESULTS
  Among 240 patients in the safety analysis, repinotan was well-tolerated, with adverse events appearing more frequently in the highest dose group (2.5 mg/d). The most common adverse event was headache (21.3% to 35% with repinotan and 24.1% with placebo). Most (75%) adverse events were of mild or moderate severity. The most common severe adverse events were neurological worsening, cerebral hemorrhage, and brain edema. The number of deaths and serious adverse events were similar among placebo and repinotan groups. Compared to the placebo group, the proportion of patients with good outcomes at three months was greatest in the group receiving repinotan 1.25 mg/d, although the difference was not statistically significant.
  
  
  CONCLUSIONS
  This study indicates that the incidence of adverse events was comparable with all doses of repinotan and placebo, and no safety issues were observed. A trend toward better tolerability with evidence of efficacy was observed with the repinotan 1.25 mg/d dose.
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Teal
authors.forename: Frank L
authors.initials: FL
authors.lastname: Silver
authors.forename: Denis
authors.initials: D
authors.lastname: Simard
mesh_terms: D000368:Aged; D001578:Benzopyrans / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007262:Infusions, Intravenous; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D020521:Stroke / Q000188:drug therapy*; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D001578:Benzopyrans; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; C111221:repinotan hydrochloride