Official Title: “Investigation of Drug-Drug Interaction Between Clopidogrel and Fluoxetine”

Clopidogrel is a platelet aggregation inhibitor witch prevents thrombotic events in patients with atherosclerotic vascular disease. To date, 4 to 30 % of patients are considered as poor, low or non-responder to this therapeutic. However, drug-drug interactions may lead to decrease the clopidogrel responsiveness. Many arguments are in support to a drug-drug interaction between clopidogrel and fluoxetine (selective serotonin reuptake inhibitor). On the pharmacokinetic level, fluoxetine inhibits the cytochroms involved in the production of clopidogrel active metabolite. On the pharmacodynamic level fluoxetine could increase the risk of hemorrhage by inhibiting the serotonin platelet reuptake and thus enhance the antiplatelet effect of clopidogrel. The purpose of this study is to investigate the influence of fluoxetine on pharmacokinetic and pharmacodynamic of clopidogrel.

Study Type: Interventional

Study Design: Other, Randomized, Single Blind (Outcomes Assessor), Uncontrolled, Crossover Assignment, Pharmacokinetics/Dynamics Study

Study Primary Completion Date: May 2009

Intervention(s) in this Clinical Trial

• Drug: Clopidogrel then fluoxetine+clopidogrel
  • D1 : clopidogrel (Plavix) 600mg (8 tablets) one time D45 to D48 : Fluoxetine (Fluoxetine EG 20mg) 20mg (1 tablet) per day D49 : 20mg Fluoxetine + 600mg Clopidogrel
• Drug: Fluoxetine+clopidogrel then clopidogrel
  • D1 to D4 : Fluoxetine (Fluoxetine EG 20mg) 20mg (1 tablet) per day D5: 20mg Fluoxetine + Clopidogrel (Plavix) 600mg (8 tablets) one time D49 : Clopidogrel 600mg one time

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Clopidogrel then fluoxetine+clopidogrel
• Active Comparator: 2
  • Fluoxetine+clopidogrel then clopidogrel

Primary Measures

• Platelet aggregation inhibition measured by optical aggregometry in presence of adenosine diphosphate (ADP) 20 μmol/L and 5 μmol/L.
  • Time Frame: Before first fluoxetin taking, during clopidogrel taking
    Safety Issue?: No

Secondary Measures

• Level of phosphorylated VASP (vasodilator- stimulated phosphoprotein), a good index of P2Y12 activity (platelet receptor of clopidogrel) and P-selectin by flow cytometry.
  • Time Frame: Before first Fluoxetine taking and during Clopidogrel taking
    Safety Issue?: No
• Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method
  • Time Frame: During clopidogrel taking
    Safety Issue?: No

Inclusion Criteria:

• Signed an informed consent
• Body mass: 60 to 85 Kg
• Platelet count: 180 to 350 G/L
• % platelet aggregation > 70%
• Subjects are to be in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results including liver function, renal and full blood count

Exclusion Criteria:

• Subject with an history of seizure disorder
• Subject with a known allergy fluoxetine or clopidogrel
• Cigarette smoking
• Subject with a history of hemorrhagic disease
• Peptic ulcer
• Psychiatric disorders
• Participation in another clinical or device trial within the three previous months
• Subject who is currently taking medications
• Subject who is currently taking medications for depression
• Subject with an history of depression (MADRS score < 15)
• Hepatic insufficiency

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 35 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Overall Clinical Trial Officials and Contacts

Pierre GARNIER, MD Principal Investigator CHU de Saint-Etienne  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00732290

Study ID Number: 0801068

ClinicalTrials.gov Identifier: NCT00732290

Health Authority: France: Afssaps - French Health Products Safety Agency