Phase II Trial of the Sigma-1 Receptor Agonist Cutamesine (SA4503) for Recovery Enhancement After Acute Ischemic Stroke

I bet this hasn't made any progress toward being used in stroke hospitals. Our fucking failures of stroke associations should already have funded and run a phase III trial of this. But no, press releases are more important. We have NO stroke strategy or stroke leadership in any part of stroke and this will fall thru the cracks. 

Phase II Trial of the Sigma-1 Receptor Agonist Cutamesine (SA4503) for Recovery Enhancement After Acute Ischemic Stroke

1. Roman Urfer, PhD,
2. Hans J. Moebius, MD, PhD,
3. David Skoloudik, MD,
4. Estevo Santamarina, MD,
5. Wakao Sato,
6. Shiro Mita, PhD,
7. Keith W. Muir, MD,
8. for the Cutamesine Stroke Recovery Study Group*

+ Author Affiliations

1. 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.).

1. Correspondence to Keith W. Muir, MD, Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow G51 4TF, Scotland, United Kingdom. E-mail keith.muir@glasgow.ac.uk

Abstract

Background and Purpose—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.

Clinical Trial Registration—URL: 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).