Abstract 19821: Does the Timing of PPI Dosing Influence the Antiplatelet Effect of Clopidogrel? Results of the SPACING Study
Background: The PPI-clopidogrel (C) pharmacodynamic interaction has been highlighted by recent FDA advisory and drug spacing in healthy volunteers did not affect the interaction. PA32540 is a novel combination product of enteric-coated (EC) aspirin (325mg) and immediate-release omeprazole (40mg). The SPACING (Simultaneous or concomitant PA32540 with Clopidogrel INteraction Gauging) Study evaluated whether PA32540 would affect the antiplatelet properties of C during concomitant or spaced administration.
Methods:SPACING was a Phase1, randomized, open-label, single-center, 3-arm crossover study conducted in 30 healthy subjects. Each treatment period was separated by a 14-day washout period. Treatments were:A) C 300mg+EC aspirin 325mg on Day 1, and C 75mg + EC aspirin 325mg on Days 2–7; B) C 300mg+PA32540 on Day 1, and C 75mg+PA32540 on Days 2–7; C) PA32540 in the morning+C 300mg >10h later on Day 1 and PA32540 in the morning +C 75 mg 10h later on Days 2–7. Subjects were first randomized to Treatment A or Treatment B and then crossed over to the alternate treatment. Following a second washout period, subjects were administered Treatment C. The primary endpoint was the percent inhibition of platelet aggregation (20μM ADP) [IPA] 1h after morning dosing on Day 7 of each period. The analysis was to demonstrate the non-inferiority of PA32540+C compared to EC aspirin 325mg+C if the upper bound of a two-sided 95% confidence interval (CI) for Treatment A-Treatment B or Treatment A-Treatment C≤ the margin of 10% IPA.
Results: Concomitant PA32540 and clopidogrel administration exceeded the non-inferiority margin of 10%. However, non-inferiority was met by the 10 h spacing of PA32540 and C (Table).
Conclusions:An interaction was observed when PA32540 and C were dosed concomitantly. When PA32540 and C were dosed 10 hours apart, no interaction was observed. Further investigations of the immediate release formulation omeprazole present in PA32540 in C-treated patients are warranted.
- © 2010 by American Heart Association, Inc.