Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine (PLATINE)

• ClinicalTrials.gov Identifier: NCT00732290
• Recruitment Status: Completed
• First Posted: August 11, 2008
• Last Update Posted: March 25, 2013
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Saint Etienne

Tracking Information

• First Submitted Date: August 8, 2008
• First Posted Date: August 11, 2008
• Last Update Posted Date: March 25, 2013
• Study Start Date: February 2009
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 8, 2008): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 8, 2008)

• 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 ]
• Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method [ Time Frame: During clopidogrel taking ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine
• Official Title: Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Outcomes Assessor)
• Condition: Healthy

Intervention

• 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

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 16, 2009): 10
• Original Estimated Enrollment (submitted: August 8, 2008): 12
• Actual Study Completion Date: May 2009
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 35 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00732290
• Other Study ID Numbers: 0801068; 2008-004395-46
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
• Study Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pierre GARNIER, MD; CHU de Saint-Etienne

• PRS Account: Centre Hospitalier Universitaire de Saint Etienne
• Verification Date: March 2013