http://stroke.ahajournals.org/content/early/2014/09/30/STROKEAHA.114.005835.abstract?
- Roman Urfer, PhD,
- Hans J. Moebius, MD, PhD,
- David Skoloudik, MD,
- Estevo Santamarina, MD,
- Wakao Sato,
- Shiro Mita, PhD,
- Keith W. Muir, MD,
- for the Cutamesine Stroke Recovery Study Group*
+ Author Affiliations
- 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).
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