Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

This study is currently recruiting participants.

Verified by Assistance Publique - Hôpitaux de Paris, July 2007

First Received: December 19, 2006 Last Updated: July 16, 2007 History of Changes

Sponsor:	Assistance Publique - Hôpitaux de Paris
Collaborators:	Centre d’investigations cliniques, HEGP Service d’hématologie biologique, HEGP Service de pharmacologie, Pitié-Salpétrière
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00413608

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 I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Influence of CYP2C19 Genetic Variants on Clopidogrel in Healthy Subjects

Resource links provided by NLM:

Drug Information available for: Clopidogrel Clopidogrel Bisulfate

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 ]
baseline and at the end of the each period [ Time Frame: during 7 days ]

Secondary Outcome Measures:

Clopidogrel and metabolites pharmacokinetics and relation to dynamics [ Time Frame: during 7 days ]

Estimated Enrollment:	30
Study Start Date:	January 2007
Estimated Study Completion Date:	April 2009

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

Contacts

Contact: Jean Sébastien HULOT, MD

. +33(0)-1-42-16-16-71

jean-sebastien.hulot@psl.aphp.fr

Locations

France
Hôpital Européen Georges Pompidou	Recruiting
PARIS, France, 75015
Contact: Jean Sébastien HULOT, MD +33(0)-1-42-16-16-71 jean-sebastien.hulot@psl.aphp.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Centre d’investigations cliniques, HEGP

Service d’hématologie biologique, HEGP

Service de pharmacologie, Pitié-Salpétrière

Investigators

Principal Investigator:

Jean Sébastien HULOT, MD

Assistance Publique - Hôpitaux de Paris

More Information

Publications:

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. Epub 2006 Jun 13.

Study ID Numbers:	P060309
Study First Received:	December 19, 2006
Last Updated:	July 16, 2007
ClinicalTrials.gov Identifier:	NCT00413608 History of Changes
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:

Therapeutic Uses
Clopidogrel
Hematologic Agents
Platelet Aggregation Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 08, 2010