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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: CLOPIDOGREL; Drug: placebo

• Registration Number: NCT01123824
• Lead Sponsor: Sanofi

Brief Summary

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

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

Study Timeline

• Study Start: 2009-04
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Study First Submitted: 2010-05-12
• Study First Submitted QC: 2010-05-13
• Study First Posted: 2010-05-14
• Status Verified: 2011-12
• Last Update Submitted: 2011-12-14
• Last Update Posted: 2011-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence clopidogrel 600/150 mg - 300/75 mg	CLOPIDOGREL	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
Sequence clopidogrel 600/150 mg - 300/75 mg	placebo	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
Sequence clopidogrel 300/75 mg - 600/150 mg	placebo	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
Sequence clopidogrel 300/75 mg - 600/150 mg	CLOPIDOGREL	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

Primary Outcome Measures

Name	Time	Method
Maximum platelet aggregation intensity (MAI) induced by Adenosine diphosphate (ADP) 5 µM after 5 days treatment	Day 5 of each period

Secondary Outcome Measures

Name	Time	Method
Maximum platelet aggregation intensity (MAI) induced by ADP 20 µM after 5 days treatment	Day 5 of each period
Clopidogrel active metabolite pharmacokinetic parameters (Cmax, tmax, AUC0-24, AUClast) after 5 days treatment	Up to 24 hours postdose on Day 5 for each period
Platelet reactivity index -Vasodilator-stimulated phosphoprotein test (PRI-VASP) after 5 days treatment	Day 5 of each period

Trial Locations

Locations (1)

Sanofi-Aventis Administrative Office; 🇩🇪 Berlin, Germany