Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Clopidogrel then fluoxetine+clopidogrel; Drug: Fluoxetine+clopidogrel then clopidogrel

• Registration Number: NCT00732290
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

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 available

Study Timeline

• Study First Submitted: 2008-08-08
• Study First Submitted QC: 2008-08-08
• Study First Posted: 2008-08-11
• Study Start: 2009-02
• Primary Completion: 2009-05
• Study Completion: 2009-05
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-22
• Last Update Posted: 2013-03-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	Clopidogrel then fluoxetine+clopidogrel	Clopidogrel then fluoxetine+clopidogrel
2	Fluoxetine+clopidogrel then clopidogrel	Fluoxetine+clopidogrel then clopidogrel

Primary Outcome Measures

Name	Time	Method
Platelet aggregation inhibition measured by optical aggregometry in presence of adenosine diphosphate (ADP) 20 μmol/L and 5 μmol/L.	Before first fluoxetin taking, during clopidogrel taking

Secondary Outcome Measures

Name	Time	Method
Level of phosphorylated VASP (vasodilator- stimulated phosphoprotein), a good index of P2Y12 activity (platelet receptor of clopidogrel) and P-selectin by flow cytometry.	Before first Fluoxetine taking and during Clopidogrel taking
Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method	During clopidogrel taking

Trial Locations

Locations (1)

Service de Medecin et Therapeutique, Unite de Recherche Clinique Groupe de Recherche sur la Thrombose (EA3065); 🇫🇷 Saint-Etienne, France