Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Clopidogrel

• Registration Number: NCT00413608
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2006-12-19
• Study First Submitted QC: 2006-12-19
• Study First Posted: 2006-12-20
• Study Start: 2007-01
• Status Verified: 2007-07
• Primary Completion: 2009-01
• Study Completion: 2009-01
• Last Update Submitted: 2011-05-04
• Last Update Posted: 2011-05-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 140

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Clopidogrel	Clopidogrel
2	Clopidogrel	Clopidogrel

Primary Outcome Measures

Name	Time	Method
Inhibition platelet activity index (ADP induced aggregation) measured between	during 7 days

Secondary Outcome Measures

Name	Time	Method
Clopidogrel and metabolites pharmacokinetics and relation to dynamics	during 7 days

Trial Locations

Locations (1)

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France