Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine

NCT00732290 | Completed Phase 1

• 2 other identifiers: 08010682008-004395-46
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy volunteer; Pharmacokinetic; pharmacodynamic; Polymorphism, Genetic

Outcome Measures

Primary Outcomes (1)

• Platelet aggregation inhibition measured by optical aggregometry in presence of adenosine diphosphate (ADP) 20 μmol/L and 5 μmol/L.

  Before first fluoxetin taking, during clopidogrel taking

Secondary Outcomes (2)

• Level of phosphorylated VASP (vasodilator- stimulated phosphoprotein), a good index of P2Y12 activity (platelet receptor of clopidogrel) and P-selectin by flow cytometry.

  Before first Fluoxetine taking and during Clopidogrel taking

• Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method

  During clopidogrel taking

Study Arms (2)

1

ACTIVE COMPARATOR

Clopidogrel then fluoxetine+clopidogrel

Drug: Clopidogrel then fluoxetine+clopidogrel

2

ACTIVE COMPARATOR

Fluoxetine+clopidogrel then clopidogrel

Drug: Fluoxetine+clopidogrel then clopidogrel

Interventions

Clopidogrel then fluoxetine+clopidogrel DRUG

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

1

Fluoxetine+clopidogrel then clopidogrel DRUG

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

2

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead

Study Sites (1)

Service de Medecin et Therapeutique, Unite de Recherche Clinique Groupe de Recherche sur la Thrombose (EA3065)

Saint-Etienne, 42055, France

Location

Study Officials

• Pierre GARNIER, MD

  CHU de Saint-Etienne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2008
• First Posted: August 11, 2008
• Study Start: February 1, 2009
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: March 25, 2013

Record last verified: 2013-03

Locations

FR (1)