Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00413608
Recruitment Status : Completed
First Posted : December 20, 2006
Last Update Posted : May 5, 2011
Information provided by:
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

Condition or disease Intervention/treatment Phase
Healthy Drug: Clopidogrel Phase 1

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects
Study Start Date : January 2007
Actual Primary Completion Date : January 2009
Actual Study Completion Date : January 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
Drug: Clopidogrel

Experimental: 2
Drug: Clopidogrel

Primary Outcome Measures :
  1. Inhibition platelet activity index (ADP induced aggregation) measured between [ Time Frame: during 7 days ]

Secondary Outcome Measures :
  1. Clopidogrel and metabolites pharmacokinetics and relation to dynamics [ Time Frame: during 7 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00413608

Hôpital Européen Georges Pompidou
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Principal Investigator: Jean Sébastien HULOT, MD Assistance Publique - Hôpitaux de Paris

Publications of Results:
Responsible Party: Yannick VACHER, Department Clinical Research of developpement Identifier: NCT00413608     History of Changes
Other Study ID Numbers: P060309
First Posted: December 20, 2006    Key Record Dates
Last Update Posted: May 5, 2011
Last Verified: July 2007

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Platelet Aggregation/drug effects
Platelet Aggregation Inhibitors/*pharmacology
Platelet Function Tests
*Polymorphism, Genetic
Ticlopidine/*analogs & derivatives/pharmacology
Healthy subjects

Additional relevant MeSH terms:
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors