Clinical trial NCT00413608: Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects
Official title: Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
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
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2006-12-20
Enrollment: 140
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Inhibition platelet activity index (ADP induced aggregation) measured between
timeFrame: during 7 days
Secondary outcomes:
measure: Clopidogrel and metabolites pharmacokinetics and relation to dynamics
timeFrame: during 7 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean Sébastien HULOT, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006 Oct 1;108(7):2244-7. doi: 10.1182/blood-2006-04-013052. Epub 2006 Jun 13.