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

A Randomized, Double-blind, Double-dummy, Two Period, Two Treatment Cross-over Pharmacodynamic and Pharmacokinetic Study of Clopidogrel Given as 5-day Repeated Oral Doses (300 mg Loading Dose Followed by 75 mg/Day and 600 mg Loading Dose Followed by 150 mg/Day) in 4 Different Groups of CYP2C19 Genotyped Healthy Male and Female Subjects

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

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

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.