Investigation of Drug-Drug Interaction Between Clopidogrel and Fluoxetine - Full Text View

Sponsored by:	Centre Hospitalier Universitaire de Saint Etienne
Information provided by:	Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:	NCT00732290

Purpose

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.

Condition	Intervention	Phase
Healthy	Drug: Clopidogrel then fluoxetine+clopidogrel Drug: Fluoxetine+clopidogrel then clopidogrel	Phase I

Drug Information available for: Fluoxetine Clopidogrel Clopidogrel Bisulfate Fluoxetine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Open Label, Uncontrolled, Crossover Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Investigation of Drug-Drug Interaction Between Clopidogrel and Fluoxetine

Further study details as provided by Centre Hospitalier Universitaire de Saint Etienne:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]
Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method [ Time Frame: During clopidogrel taking ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	March 2009
Estimated Study Completion Date:	November 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Clopidogrel then fluoxetine+clopidogrel	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
2: Active Comparator Fluoxetine+clopidogrel then 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

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732290

Contacts

Contact: Pierre GARNIER, MD	+33 (0)4 77 12 77 88	pierre.garnier@chu-st-etienne.fr
Contact: Arnauld GARCIN, CRA	+33 (0)4 77 82 83 00	agarcin34@yahoo.fr

Locations

France
Service de Medecin Interne et Therapeutique Unite de Recherche Clinique Groupe de Recherche sur la Thrombose (EA3065)
Saint-Etienne, France, 42055

Sponsors and Collaborators

Centre Hospitalier Universitaire de Saint Etienne

Investigators

Principal Investigator:

Pierre GARNIER, MD

CHU de Saint-Etienne

More Information

Responsible Party:	CHU de Saint-Etienne ( Françoise LORCA )
Study ID Numbers:	2008-004395-46, 0801068
Study First Received:	August 8, 2008
Last Updated:	October 29, 2008
ClinicalTrials.gov Identifier:	NCT00732290
Health Authority:	France: Afssaps - French Health Products Safety Agency; France: French Data Protection Authority

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:

Healthy volunteer
Pharmacokinetic
pharmacodynamic
Polymorphism, Genetic

Study placed in the following topic categories:

Fluoxetine
Clopidogrel
Healthy
Serotonin

Additional relevant MeSH terms:

Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hematologic Agents
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Uptake Inhibitors

Pharmacologic Actions
Serotonin Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on January 16, 2009