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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:
NCT00732290
First received: August 8, 2008
Last updated: March 22, 2013
Last verified: March 2013
  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:


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 November 20, 2014