Abstract 15852: Platelet Inhibition With PA32540 (a Tablet of Enteric-Coated Aspirin and Immediate-Release Omeprazole ) + Clopidogrel Dosed Separately is Greater Than Enteric-Coated Aspirin + Enteric-Coated Omeprazole + Clopidogrel Dosed Synchronously: Results of a Randomized, Open-Label, Cross-Over Study
Background: PA32540 is a novel combination product of enteric-coated (EC) aspirin (ASA) and immediate-release (IR) omeprazole intended for secondary prevention of cardiovascular events in patients at risk for developing ASA-induced gastric ulcers. It has been reported that spacing EC omeprazole and clopidogrel administration does not affect the pharmacodynamic (PD) interaction. The unique IR formulation of omeprazole in PA32540 may lead to a different interaction than reported with EC omeprazole. In the present study (the Co-Rx study), we compared the PD response of EC omeprazole + dual antiplatelet therapy (DAPT) administered synchronously vs. PA32540 + clopidogrel administered separately (10 hours apart).
Methods: A Phase 1, randomized, open-label, single-center, crossover study was conducted in 30 healthy subjects age 40 years or older. Treatment periods were 7 days in duration separated by a 14-day washout period. Treatment A) PA32540 in the morning + clopidogrel 300 mg loading/ 75 mg maintenance at least 10 hours later; Treatment B) Synchronous dosing of 300 mg clopidogrel loading/ 75 mg maintenance + EC ASA 81 mg + EC omeprazole 40 mg. Light transmittance aggregometry [20 μ M ADP and 2 mM arachidonic acid (AA)] was measured at baseline and Day 7. The primary endpoint was inhibition of platelet aggregation (IPA) at Day 7 using 20 μ M ADP as agonist. IPA between Treatment A and Treatment B were compared using analysis of covariance.
Results: IPA was greater with spaced PA32540 + clopidogrel therapy vs. synchronous clopidogrel + EC ASA + EC omeprazole therapy (p = 0.004). There was no difference in Day 7 AA-induced aggregation.
Conclusions: PA32540, with a novel IR formulation of omeprazole, when dosed at least 10 hours apart from clopidogrel, significantly lessens the PD interaction with clopidogrel compared to a standard regimen. These finding are directly relevant to the treatment of patients with high gastrointestinal risk who require DAPT and gastroprotection.
- © 2011 by American Heart Association, Inc.