Clinical trial NCT00732290: Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine
Official title: Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteer
Pharmacokinetic
pharmacodynamic
Polymorphism, Genetic
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
First posted: 2008-08-11
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.


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

Primary outcomes:
measure: Platelet aggregation inhibition measured by optical aggregometry in presence of adenosine diphosphate (ADP) 20 μmol/L and 5 μmol/L.
timeFrame: Before first fluoxetin taking, during clopidogrel taking
Secondary outcomes:
measure: Level of phosphorylated VASP (vasodilator- stimulated phosphoprotein), a good index of P2Y12 activity (platelet receptor of clopidogrel) and P-selectin by flow cytometry.
timeFrame: Before first Fluoxetine taking and during Clopidogrel taking
measure: Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method
timeFrame: During clopidogrel taking
Other outcomes:
Locations:
city: Saint-Etienne
country: France
facility: Service de Medecin et Therapeutique, Unite de Recherche Clinique Groupe de Recherche sur la Thrombose (EA3065)
Study officials:
affiliation: CHU de Saint-Etienne
name: Pierre GARNIER, MD
role: PRINCIPAL_INVESTIGATOR
References: