NDLI: Impact of a fixed-dose combination of naproxen and esomeprazole magnesium on serum thromboxane B2 inhibition by low-dose aspirin over 5 days in healthy adults: a phase I, randomized, double-blind, placebo-controlled, noninferiority trial.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Angiolillo, Dominick J. Hwang, Clara Datto, Catherine Desai, Bhaloo Sostek, Mark
Spatial Coverage	United States
Description	Country affiliation: United States Author Affiliation: Angiolillo DJ ( University of Florida College of Medicine-Jacksonville, Jacksonville, Florida 32209, USA. dominick.angiolillo@jax.ufl.edu)
Abstract	BACKGROUND: Low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) are often used concomitantly; however, some NSAIDs may interfere with LDA antiplatelet activity. OBJECTIVE: We evaluated the impact of coadministered enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg (fixed-dose combination) on LDA-mediated platelet cyclooxygenase (COX)-1 inhibition. METHODS: In this Phase I, single-center, double-blind, placebo-controlled study, healthy volunteers (50-75 years) received enteric-coated LDA 81 mg once daily (QD) on days 1 to 5 (open-label), then enteric-coated LDA 81 mg QD plus either naproxen/esomeprazole magnesium or placebo twice daily (BID) on days 6 to 10 (randomized). Serum thromboxane B(2) (TXB(2)) inhibition from baseline to day 11 was the primary end point. The primary analysis excluded volunteers with ≤95% inhibition at day 6. Assay sensitivity and noninferiority of naproxen/esomeprazole magnesium versus placebo were concluded if the 90% CI lower limit for percent inhibition of TXB(2) was >90.0% in both treatment groups (prespecified criterion). Tolerability was a secondary end point. RESULTS: Overall, 42 volunteers were enrolled, 40 randomized, and 32 included in the primary pharmacodynamic analysis (day 6 TXB(2) inhibition ≥95%). Most volunteers (86%) were white, and 57% were female. Mean age was 60 (7) years, and mean body mass index was 26.4 (2.6) kg/m(2). Day 11 mean serum TXB(2) inhibition was 99.1% (90% CI, 98.7-99.6) in the LDA plus placebo group (n = 18) versus 99.6% (90% CI, 99.4-99.8) in the LDA plus naproxen/esomeprazole magnesium group (n = 14). Noninferiority of naproxen/esomeprazole magnesium versus placebo was established (CI lower limit >90.0%). Adverse event (AE) incidence was 40% (n = 8/20) in the LDA plus placebo group and 15% (n = 3/20) in the LDA plus naproxen/esomeprazole magnesium group. No serious AEs or discontinuations due to AEs were observed. CONCLUSIONS: This pilot investigation suggests that LDA coadministered with naproxen/esomeprazole magnesium is noninferior to LDA alone for platelet COX-1 inhibition, as measured by serum TXB(2) concentration, in healthy volunteers. ClinicalTrials.gov identifier: NCT01094483.
File Format	HTM / HTML
ISSN	01492918
Issue Number	12
Volume Number	33
e-ISSN	1879114X
Journal	Clinical Therapeutics
Language	English
Publisher	Elsevier
Publisher Date	2011-12-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Anti-inflammatory Agents, Non-steroidal Administration & Dosage Aspirin Blood Platelets Drug Effects Cyclooxygenase 1 Blood Cyclooxygenase Inhibitors Esomeprazole Naproxen Platelet Aggregation Inhibitors Proton Pump Inhibitors Thromboxane B2 Aged Adverse Effects Enzymology Double-blind Method Drug Combinations Female Humans Male Middle Aged Pilot Projects Placebos Tablets, Enteric-coated Time Factors United States Clinical Trial, Phase I Comparative Study Journal Article Randomized Controlled Trial
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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