title: Phase II trial of the Sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke.
abstract: OBJECTIVE
  The σ-1 receptor (Sig-1R) agonist cutamesine (SA4503) enhanced functional recovery after experimental stroke with a treatment initiation window of 48 hours and chronic treatment for 28 days. We conducted a phase 2 clinical trial exploring the safety, tolerability, dose range, and functional effects of cutamesine in patients with ischemic stroke.
  
  
  METHODS
  Subjects were randomized between 48 and 72 hours after stroke to receive cutamesine 1 mg/d, 3 mg/d, or placebo for 28 days. Effects on safety and function were assessed at baseline, at end of treatment (day 28), and at end of follow-up (day 56).
  
  
  RESULTS
  In 60 patients, treatment with both cutamesine dosages was safe and well tolerated without significant differences in numbers of treatment emergent or serious adverse events. No significant effect was observed on the primary efficacy measure (change in National Institutes of Health Stroke Scale from baseline to day 56) or modified Rankin Scale and Barthel Index scores. Post hoc analysis of moderately and severely affected patients (baseline National Institutes of Health Stroke Scale, ≥7 and ≥10) showed greater National Institutes of Health Stroke Scale improvements in the 3 mg/d cutamesine group when compared with placebo (P=0.034 and P=0.038, respectively). A trend toward a higher proportion being able to complete a 10m timed walk was observed for cutamesine-treated subjects.
  
  
  CONCLUSIONS
  Cutamesine was safe and well tolerated at both dosage levels. Although no significant effects on functional end points were seen in the population as a whole, greater improvement in National Institutes of Health Stroke Scale scores among patients with greater pretreatment deficits seen in post hoc analysis warrants further investigation. Additional studies should focus on the patient population with moderate-to-severe stroke.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov/show/NCT00639249. Unique identifier: NCT00639249. The EudraCT number is 2007-004840-60 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004840-60/GB).
authors.affiliation: From the M's Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.).
authors.forename: Roman
authors.initials: R
authors.lastname: Urfer
authors.affiliation: From the M's Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.).
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Moebius
authors.affiliation: From the M's Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.).
authors.forename: David
authors.initials: D
authors.lastname: Skoloudik
authors.affiliation: From the M's Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.).
authors.forename: Estevo
authors.initials: E
authors.lastname: Santamarina
authors.affiliation: From the M's Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.).
authors.forename: Wakao
authors.initials: W
authors.lastname: Sato
authors.affiliation: From the M's Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.).
authors.forename: Shiro
authors.initials: S
authors.lastname: Mita
authors.affiliation: From the M's Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.). keith.muir@glasgow.ac.uk.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002250:Carbon Radioisotopes / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D011877:Radionuclide Imaging; D017480:Receptors, sigma / Q000819:agonists*; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000000981:diagnostic imaging* / Q000503:physiopathology; D013997:Time Factors; D000097605:Sigma-1 Receptor
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C101789:SA 4503
keywords: SA 4503; clinical trial; randomized controlled trial; stroke