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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Clopidogrel then fluoxetine+clopidogrel; Drug: Fluoxetine+clopidogrel then clopidogrel	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Single (Outcomes Assessor)
Official Title:	Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine
Study Start Date :	February 2009
Actual Primary Completion Date :	May 2009
Actual Study Completion Date :	May 2009

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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 ]
2. Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method [ Time Frame: During clopidogrel taking ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 35 Years (Adult)
Sexes 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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:	NCT00732290 History of Changes
Other Study ID Numbers:	0801068; 2008-004395-46
First Posted:	August 11, 2008
Last Update Posted:	March 25, 2013
Last Verified:	March 2013

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:

Healthy volunteer; Pharmacokinetic; pharmacodynamic; Polymorphism, Genetic

Additional relevant MeSH terms:

Clopidogrel; Ticlopidine; Fluoxetine; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Fibrinolytic Agents	Fibrin Modulating Agents; Cytochrome P-450 CYP2C19 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors