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

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 1


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:

MedlinePlus related topics: Drug Reactions

Drug Information available for: Fluoxetine Fluoxetine hydrochloride 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:	Centre Hospitalier Universitaire 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:	March 22, 2013
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: French Data Protection Authority

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:


Healthy volunteer Pharmacokinetic pharmacodynamic Polymorphism, Genetic

Additional relevant MeSH terms:


Clopidogrel Fluoxetine Ticlopidine Antidepressive Agents Antidepressive Agents, Second-Generation Cardiovascular Agents Central Nervous System Agents Fibrin Modulating Agents Fibrinolytic Agents Hematologic Agents Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents	Neurotransmitter Uptake Inhibitors Pharmacologic Actions Physiological Effects of Drugs Platelet Aggregation Inhibitors Psychotropic Drugs Purinergic Agents Purinergic Antagonists Purinergic P2 Receptor Antagonists Purinergic P2Y Receptor Antagonists Serotonin Agents Serotonin Uptake Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015

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