Pharmacodynamic and Pharmacokinetic Study of 2 Different Dose Regimen of Clopidogrel in CYP2C19 Genotyped Healthy Subjects

NCT ID: NCT01123824

Last Updated: 2011-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2009-08-31

Brief Summary

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Primary Objective:

* Investigate the possible role of the CYP2C19 genotype in Adenosine diphosphate (ADP)-induced platelet aggregation after administration of a standard dose regimen of clopidogrel (300 mg loading dose followed by 75 mg/day for 4 days) in healthy male and female subjects

Secondary Objectives:

* Assess the pharmacodynamic activity of a higher dose regimen of clopidogrel (600 mg loading dose followed by 150 mg/day for 4 days)
* Compare the pharmacokinetic profiles of clopidogrel active metabolite between the selected groups of genotyped subjects and the 2 dose regimen

Detailed Description

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The total study duration per subject is 10-12 weeks broken down as follows:

* Screening: 2 to 40 days before the first dosing
* Period 1: 7 days including 5 days treatment
* Washout: At least 14 days after the last dosing
* Period 2: 7 days including 5 days treatment
* End of study: 7 to 10 days after the last dosing

Conditions

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Healthy

Keywords

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healthy subjects

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Sequence clopidogrel 300/75 mg - 600/150 mg

Period 1:

* Day 1: clopidogrel, 300 mg loading dose + placebo
* Day 2 to Day 5: clopidogrel, 75 mg + placebo, once daily

Period 2:

* Day 1: clopidogrel, 600 mg loading dose
* Day 2 to Day 5: clopidogrel, 150 mg, once daily

Each intake is at around 8:00 AM fasted for at least 10 hours

Group Type EXPERIMENTAL

CLOPIDOGREL

Intervention Type DRUG

Pharmaceutical form: tablets

Route of administration: oral

placebo

Intervention Type DRUG

Pharmaceutical form: matching tablets

Route of administration: oral

Sequence clopidogrel 600/150 mg - 300/75 mg

Period 1:

* Day 1: clopidogrel, 600 mg loading dose
* Day 2 to Day 5: clopidogrel, 150 mg, once daily

Period 2:

* Day 1: clopidogrel, 300 mg loading dose + placebo
* Day 2 to Day 5: clopidogrel, 75 mg + placebo, once daily

Each intake is at around 8:00 AM fasted for at least 10 hours

Group Type EXPERIMENTAL

CLOPIDOGREL

Intervention Type DRUG

Pharmaceutical form: tablets

Route of administration: oral

placebo

Intervention Type DRUG

Pharmaceutical form: matching tablets

Route of administration: oral

Interventions

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CLOPIDOGREL

Pharmaceutical form: tablets

Route of administration: oral

Intervention Type DRUG

placebo

Pharmaceutical form: matching tablets

Route of administration: oral

Intervention Type DRUG

Other Intervention Names

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SR25990

Eligibility Criteria

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Inclusion Criteria

Healthy subject in good health, as determined by a medical history, physical examination including vital signs and clinical laboratory tests:

* with a body weight between 45 kg and 95 kg if male, between 40 kg and 85 kg if female, and with a Body Mass Index (BMI) between 18 and 30 kg/m²
* classified into one of the 4 groups of metabolizers according to his/her CYP2C19 genotype:

* Ultrarapid Metabolizers (UMs, CYP2C19\*1/\*17 and CYP2C19\*17/\*17)
* homozygous Extensive Metabolizers (homoEMs, CYP2C19\*1/\*1)
* heterozygous Extensive Metabolizers (heteroEMs, CYP2C19\*1/\*2 and CYP2C19\*1/\*3)
* Poor Metabolizers (PMs, CYP2C19\*2/\*2 and CYP2C19\*2/\*3)

Exclusion Criteria

* Evidence of inherited disorder of coagulation/hemostasis functions
* Subject smoking more than 10 cigarettes or equivalent per day
* Unability to abstain from intake of any drug affecting hemostasis throughout the whole study duration

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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International Clinical Development Study Director

Role: STUDY_CHAIR

Sanofi

Locations

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Sanofi-Aventis Administrative Office

Berlin, , Germany

Site Status

Countries

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Germany

References

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Simon T, Bhatt DL, Bergougnan L, Farenc C, Pearson K, Perrin L, Vicaut E, Lacreta F, Hurbin F, Dubar M. Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clin Pharmacol Ther. 2011 Aug;90(2):287-95. doi: 10.1038/clpt.2011.127. Epub 2011 Jun 29.

Reference Type RESULT
PMID: 21716274 (View on PubMed)

Other Identifiers

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2009-010105-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PKD11147

Identifier Type: -

Identifier Source: org_study_id