Healthy
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGClopidogrel
Clopidogrel
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Inhibition platelet activity index (ADP induced aggregation) measured between | during 7 days |
Secondary
| Measure | Time frame |
|---|---|
| Clopidogrel and metabolites pharmacokinetics and relation to dynamics | during 7 days |
Countries
France
Outcome results
None listed