Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

This study has been completed.
Information provided by:
Assistance Publique - Hôpitaux de Paris Identifier:
First received: December 19, 2006
Last updated: May 4, 2011
Last verified: July 2007
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 Intervention Phase
Drug: Clopidogrel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

Resource links provided by NLM:

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Inhibition platelet activity index (ADP induced aggregation) measured between [ Time Frame: during 7 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clopidogrel and metabolites pharmacokinetics and relation to dynamics [ Time Frame: during 7 days ] [ Designated as safety issue: Yes ]

Enrollment: 140
Study Start Date: January 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Drug: Clopidogrel
Experimental: 2
Drug: Clopidogrel

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.

Ages Eligible for Study:   18 Years to 35 Years
Genders 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
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Please refer to this study by its identifier: 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
  More Information

Responsible Party: Yannick VACHER, Department Clinical Research of developpement Identifier: NCT00413608     History of Changes
Other Study ID Numbers: P060309
Study First Received: December 19, 2006
Last Updated: May 4, 2011
Health Authority: France: Ministry of Health

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
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses processed this record on November 27, 2015