Takeda Global Research & Development Center, Inc., U.S., (TGRD U.S.) announced today that it has initiated a trial to study how dexlansoprazole and several other proton pump inhibitors (PPIs) affect the pharmacokinetics and pharmacodynamics of Plavix (clopidogrel bisulfate) in healthy subjects. Takeda has been evaluating all published data and communications from the U.S. Food and Drug Administration (FDA) regarding the potential risks associated with concomitant use of clopidogrel and PPIs.
This clinical trial, titled "A Study of the Effects of Multiple Doses of Dexlansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Subjects," is currently enrolling subjects and is expected to be completed within the 2010 calendar year. The randomized, open-label, single-center, multiple-dose, 2-period, crossover study is designed to assess the effects of multiple oral doses of four once-daily PPIs on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy subjects. Clopidogrel is a drug that is indicated for the reduction of atherothrombotic events, such as recent myocardial infarction, recent stroke, established peripheral arterial disease, or acute coronary syndrome.
According to a recent FDA announcement, studies have shown that omeprazole inhibits a liver enzyme (CYP2C19) important for the activation of clopidogrel. With CYP2C19 inhibition, clopidogrel will have reduced anticlotting effects, thereby reducing its effectiveness. The FDA has recommended that co-administration of omeprazole and other potent CYP2C19 inhibitors, including esomeprazole, be avoided in patients taking clopidogrel. It is unknown how other PPIs may interfere with Plavix.