Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

Study Overview
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Brief Summary
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To test pharmacodynamic response to clopidogrel 150mg once daily during 7 days in healthy subjects carriers of a mutated allele (*2) associated with CYP2C19 deficiency and non responders to the usual regimen of 75 mg once daily

Detailed Description
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Thirty individuals genotyped for specific variants of 2C19 cytochrome and P2Y12 platelet ADP receptor will receive during one week a daily dose of 75 mg of clopidogrel. Depending on their pharmacodynamic response to this dose of clopidogrel, subjects will be affiliated to two groups, good responders and bad responders. After a wash-out period, bad responders will receive a double dose of clopidogrel, while the good responders will receive 75 mg of clopidogrel, associated with a CYP2C19 inhibitor. Such study will allow to evaluate both the impact of raising daily dose of clopidogrel in patients with defected variants of 2C19 and potential interactions of clopidogrel with other drugs.

Official Title
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Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers, aged 18 to 35, non smoker, of caucasian origin Compatible 2C19 and P2Y12 genotypes Weight 60 kg to 100 kg, and normal BMI Standard laboratory investigations normal Negative testing for HIV infection and B and C hepatitis Basal platelet agregation testing normal EKG, blood pressure and cardiac frequency in normal range Ability to understand, follow and sign the protocol Exclusion Criteria: Evolutive medical affection, even treated Medical history of allergic response to medication or other, peptic ulcer, or known hemorrhagic disorder Laboratory testing out of normal range Subjects practicing violent sports Unability to understand or follow the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Clopidogrel | Drug: Clopidogrel<br>* Clopidogrel<br>|
| Experimental: 2<br>Clopidogrel | Drug: Clopidogrel<br>* Clopidogrel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition platelet activity index (ADP induced aggregation) measured between |  | during 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clopidogrel and metabolites pharmacokinetics and relation to dynamics |  | during 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human, Adults, Male, Alleles, Genotype, Platelet Aggregation/drug effects, Platelet Aggregation Inhibitors/*pharmacology, Platelet Function Tests, Pharmacogenetics, *Polymorphism, Genetic, Ticlopidine/*analogs & derivatives/pharmacology, Healthy subjects