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document
Gastrointestinal safety of NO-aspirin ( NCX-4016 ) in healthy human volunteers : a proof of concept endoscopic study . BACKGROUND AND AIMS NCX-4016 is a nitric oxide-releasing derivative of aspirin with antiplatelet activity . The aim of this study was to investigate the effect of NCX-4016 on gastrointestinal mucosa and platelet functions in healthy human volunteers . METHODS This was a parallel-group , double-blind , placebo-controlled study . Forty healthy subjects were randomly allocated to receive 7 days of treatment with NCX-4016 ( 400 and 800 mg twice daily ) , equimolar doses of aspirin ( 200 and 420 mg twice daily ) , or placebo . Upper endoscopies were performed before and at the end of the treatment period , and gastroduodenal lesions were graded using a predefined scoring system . Basal and posttreatment platelet aggregation in response to arachidonic acid ( AA ) and serum thromboxane ( TX ) B ( 2 ) and AA-stimulated platelet TXB ( 2 ) production were investigated . RESULTS Mucosal endoscopic injury score on day 7 was 0.63 +/- 0.16 in the placebo group and 11.0 +/- 3.0 and 16.1 +/- 1.6 in healthy volunteers treated with 200 and 420 mg aspirin twice daily ( P < 0.0001 vs. placebo ) . NCX-4016 was virtually devoid of gastric and duodenal toxicity , resulting in a total gastric and duodenal endoscopic score of 1.38 +/- 0.3 and 1.25 +/- 0.5 ( P < 0.0001 vs. aspirin , not significant vs. placebo ) . NCX-4016 inhibited AA-induced platelet aggregation as well as serum TXB ( 2 ) and platelet TXB ( 2 ) generation induced by AA to the same extent as aspirin ( not significant vs. aspirin ) . CONCLUSIONS In this study , we have proven the concept that addition of an NO-donating moiety to aspirin results in a new chemical entity that maintains cyclooxygenase-1 and platelet inhibitory activity while nearly avoiding gastrointestinal damage .
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Intervention_Pharmacological
NO-aspirin ( NCX-4016 )
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Intervention_Pharmacological
NCX-4016
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Intervention_Pharmacological
NCX-4016
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Intervention_Pharmacological
NCX-4016 ( 400 and 800 mg twice daily )
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Intervention_Pharmacological
equimolar doses of aspirin ( 200 and 420 mg twice daily
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Intervention_Control
placebo
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Intervention_Pharmacological
aspirin
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Outcome_Physical
Gastrointestinal safety
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Outcome_Physical
antiplatelet activity
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Outcome_Physical
platelet functions
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Outcome_Physical
gastroduodenal lesions
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Outcome_Physical
predefined scoring system
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Outcome_Physical
Basal and posttreatment platelet aggregation
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Outcome_Physical
Mucosal endoscopic injury score
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Outcome_Adverse-effects
gastric and duodenal toxicity
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Outcome_Physical
AA-induced platelet aggregation
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Outcome_Physical
serum TXB ( 2 )
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Outcome_Physical
platelet TXB ( 2 ) generation
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Outcome_Physical
gastrointestinal damage
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Participant_Condition
healthy human
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Participant_Condition
healthy human
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Participant_Sample-size
Forty
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Participant_Condition
healthy