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Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00413608
First received: December 19, 2006
Last updated: May 4, 2011
Last verified: July 2007
History of Changes
  Purpose

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
Healthy
 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:

U.S. FDA Resources

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
Clopidogrel
 Drug: Clopidogrel
Clopidogrel
Other Name: Clopidogrel
Experimental: 2
Clopidogrel
 Drug: Clopidogrel
Clopidogrel
Other Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413608

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

Publications:

Responsible Party: Yannick VACHER, Department Clinical Research of developpement
ClinicalTrials.gov 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:
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

Additional relevant MeSH terms:
Clopidogrel
Platelet Aggregation Inhibitors
Ticlopidine
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
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
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 23, 2013