Deerfield, Ill., (February 9, 2010) –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.
“The extent to which each PPI is metabolized by the liver enzyme CYP2C19 varies. Prior to the FDA approval of dexlansoprazole, Takeda conducted a variety of in vitro and clinical studies, which suggested that dexlansoprazole is not likely to inhibit the liver enzyme CYP2C19,” said David Recker, M.D., senior vice president of clinical science for TGRD U.S. “This new study will provide clinicians with additional information regarding the interaction potential between dexlansoprazole, lansoprazole, esomeprazole, and omeprazole with clopidogrel bisulfate. It will also represent the first prospective data with dexlansoprazole and clopidogrel and add to the body of information on the concomitant use of several other PPIs and clopidogrel.”
In the interaction study, subjects will be randomized into eight regimen sequence groups, each of which will receive two regimens. The endpoints of this study are to measure plasma concentrations of the active metabolite for clopidogrel and to determine the subject’s total exposure to the active metabolite after clopidogrel has been administered with each of the PPIs for nine days. Platelet function will also be assessed prior to and during the trial, as well as 24 hours following the nine-day exposure to each PPI.
About KAPIDEX™ (dexlansoprazole) 30 mg and 60 mg delayed release capsules
KAPIDEX is a proton pump inhibitor (PPI), which decreases acid production by turning off many of the acid pumps in the stomach, thus helping to protect the esophagus from acidic reflux so that esophageal inflammation can heal. KAPIDEX combines an enantiomer of lansoprazole with a Dual Delayed Release™ (DDR) formulation designed to provide two separate releases of medication. KAPIDEX, taken once daily, is approved for the healing of all grades of erosive esophagitis (EE) for up to eight weeks, maintaining healing of EE for up to six months, and treating heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD) for four weeks.
Important Safety Information
KAPIDEX is contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity and anaphylaxis have been reported with KAPIDEX use. Symptomatic response with KAPIDEX does not preclude the presence of gastric malignancy.
The most commonly reported treatment-emergent adverse reactions (≥2%) include diarrhea (4.8%), abdominal pain (4.0%), nausea (2.9%), upper respiratory tract infection (1.9%), vomiting (1.6%), and flatulence (1.6%). KAPIDEX must not be co-administered with atazanavir because atazanavir systemic concentrations may be substantially decreased.
KAPIDEX may interfere with the absorption of drugs for which gastric pH is important for bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole). Patients taking concomitant warfarin may require monitoring for increases in international normalized ratio (INR) and prothrombin time. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Concomitant tacrolimus use may increase tacrolimus whole blood concentrations.
Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology and gastroenterology treatments and seek to bring innovative products to patients through a pipeline that includes compounds in development for diabetes, cardiovascular disease, gastroenterology, neurology and other conditions. To learn more about these Takeda companies, visit www.tpna.com.