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

Sponsor:	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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Single Blind (Outcomes Assessor)
Official Title:	Investigation of Drug-Drug Interaction Between Clopidogrel and Fluoxetine

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Drug Reactions

Drug Information available for: Fluoxetine Fluoxetine hydrochloride Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

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 ]

Enrollment:	10
Study Start Date:	February 2009
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 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
Active Comparator: 2 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

Locations

France
Service de Medecin 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

No publications provided

Responsible Party:	Clément CAILLAUX, CHU de Saint-Etienne
ClinicalTrials.gov Identifier:	NCT00732290 History of Changes
Other Study ID Numbers:	0801068, 2008-004395-46
Study First Received:	August 8, 2008
Last Updated:	June 9, 2009
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

Additional relevant MeSH terms:

Fluoxetine
Clopidogrel
Ticlopidine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents

Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Hematologic Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on February 09, 2012