22. European Stroke Conference 298 © 2013 S. Karger AG, Basel Scientific Programme 40 Acute stroke: new treatment concepts Safety, Tolerability and Pharmacokinetics of MCI-186 in Patients with Acute Ischemic Stroke: a New Dose Regimen of Bolus plus 72-Hour Intravenous Infusion M. Kaste1, S. Murayama2, T. Tatlisumak3, G. Ford4, P.J. Koudstaal5, M. Walters6 MCI-186 Study Group Helsinki University Central Hospital, Helsinki, FINLAND1, Mitsubishi Tanabe Pharma Co., To-kyo, JAPAN2, Helsinki University Central Hospital, Helsinki, FINLAND3, Newcastle University, Newcastle, UNITED KINGDOM4, University Hospital Rotterdam, Rotterdam, THE NETHER-LANDS5, University of Glasgow, Glasgow, UNITED KINGDOM6 Background and purpose MCI-186 (edaravone) is the first free radical scavenger approved (Japan 2001) for the treatment of patients with acute ischemic stroke (AIS). We investigated the safety (it was the primary outcome of the trial) and plasma levels of a new regimen (bolus plus infusion) and a new formulation of MCI-186 in patients with AIS, and the effects of the treatment on early im-provement and on 3-month outcome. Methods In a double-blind, placebo-controlled trial, 2 different dosing regimens (loading dose 0.08 mg/kg + 0.2 mg/kg/h Cohort I; loading dose 0.16 mg/kg + 0.4 mg/kg/h Cohort II) were adminis-tered in 2:1 (drug/placebo) as 72-hour IV infusion to two groups of 18 patients with AIS. Adverse events (AEs), plasma concentrations, National Institute of Health Stroke Scale (NIHSS) at 72 hours, 3-month Barthel Index (BI), Modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS) were assessed. Admission NIHSS of patients in Cohort I and II and in placebo treated patients (Co-hort PL) were 5, 5 and 6, and the mean age of patients 65, 63 and 69 years, respectively. Results There were no deaths. Two serious treatment-related AEs (TRAEs) occurred (2 gout flares in one patient of Cohort II). All other TRAEs were mild or moderate and transient; in Cohort I 6 pa-tients had 10, in Cohort II 5 patients had 7 and in Cohort PL 5 patients had 9 such TRAEs. Plasma MCI-186 therapeutic range is considered to be 250-1000 ng/mL. After the initiation of IV infusion the plasma concentration of MCI-186 reached a steady state at an aimed level within 24 hours in Cohorts I and II. At the end of 72-hour infusion the mean plasma concentrations were 391 ng/mL (Cohort I) and 1595 ng/mL (Cohort II) and declined rapidly thereafter. Patients of Cohort II showed a trend towards greater improvement of NIHSS at 72 hours and towards a better 3-month BI, mRS and GOS. Conclusions The new dose regimen was safe and well-tolerated. The results support further trials of MCI-186 in patients with AIS.
Karger_ESC London_2013
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