NXY-059 does not affect bleeding time in healthy volunteers: a randomized, double-blind, placebo-controlled, 3-period crossover phase I study.
NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale. Any effect of NXY-059 on hemostasis may be important when treating stroke patients. This phase I randomized, double-blind, placebo-controlled, 3-period crossover study compared the effect of NXY-059, desmopressin, and placebo on bleeding time, platelet aggregation, and adhesion in 30 healthy volunteers. NXY-059 did not prolong bleeding time compared with placebo: mean (SD) time for NXY-059, 369.5 seconds (125.0 seconds) versus placebo, 369.1 seconds (136.0 seconds). There were no significant effects on platelet aggregation or adhesion. At a mean unbound plasma concentration (Cu(ss)) of 335 micromol/L, NXY-059 was well tolerated, with no major safety concerns identified. In conclusion, NXY-059 does not appear to affect primary hemostasis.
Nilsson
Dag
D
Medical Neuroscience, AstraZeneca R&D, Södertälje, SE-151 85, Sweden. dag.nilsson@astrazeneca.com.
Wemer
Johan
J
Cheng
Yi-Fang
YF
Reinholdsson
Ingalill
I
Englund
Gunnar
G
Egberg
Nils
N
Schulman
Sam
S
D001557:Benzenesulfonates / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D018592:Cross-Over Studies; D003894:Deamino Arginine Vasopressin / Q000009:adverse effects / Q000494:pharmacology; D004311:Double-Blind Method; D006490:Hemostatics / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects
D001557:Benzenesulfonates; D006490:Hemostatics; D018696:Neuroprotective Agents; C120851:disufenton sodium; D003894:Deamino Arginine Vasopressin