Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00732290

Acronym

PLATINE

Enrollment

Registered

2008-08-11

Start date

2009-02-28

Completion date

2009-05-31

Last updated

2013-03-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Healthy volunteer, Pharmacokinetic, pharmacodynamic, Polymorphism, Genetic

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.

Interventions

DRUGClopidogrel 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

DRUGFluoxetine+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

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

MALE

Age

18 Years to 35 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame
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

Measure	Time frame
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

Countries

France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026