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

Sanofi

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: placebo; Drug: CLOPIDOGREL

Study type: Interventional

Funder types: Industry

Identifiers

NCT01123824

2009-010105-37 (EudraCT Number)

PKD11147

Details and patient eligibility

About

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

Full 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

Enrollment: 40 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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40 participants in 2 patient groups

Sequence clopidogrel 300/75 mg - 600/150 mg

Experimental group

Description:

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

Treatment:

Drug: placebo

Drug: CLOPIDOGREL

Sequence clopidogrel 600/150 mg - 300/75 mg

Experimental group

Description:

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

Treatment:

Drug: placebo

Drug: CLOPIDOGREL