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

NCT01123824 | Completed Phase 1

• 2 other identifiers: PKD111472009-010105-37
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy

Keywords

healthy subjects

Outcome Measures

Primary Outcomes (1)

• Maximum platelet aggregation intensity (MAI) induced by Adenosine diphosphate (ADP) 5 µM after 5 days treatment

  Day 5 of each period

Secondary Outcomes (3)

• Maximum platelet aggregation intensity (MAI) induced by ADP 20 µM after 5 days treatment

  Day 5 of each period

• Platelet reactivity index -Vasodilator-stimulated phosphoprotein test (PRI-VASP) 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

Study Arms (2)

Sequence clopidogrel 300/75 mg - 600/150 mg

EXPERIMENTAL

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

Drug: CLOPIDOGREL; Drug: placebo

Sequence clopidogrel 600/150 mg - 300/75 mg

EXPERIMENTAL

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

Drug: CLOPIDOGREL; Drug: placebo

Interventions

CLOPIDOGREL DRUG

Pharmaceutical form: tablets Route of administration: oral

Also known as: SR25990

Sequence clopidogrel 300/75 mg - 600/150 mg; Sequence clopidogrel 600/150 mg - 300/75 mg

placebo DRUG

Pharmaceutical form: matching tablets Route of administration: oral

Sequence clopidogrel 300/75 mg - 600/150 mg; Sequence clopidogrel 600/150 mg - 300/75 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sanofi-Aventis Administrative Office

Berlin, Germany

Location

Related Publications (1)

• 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.

  PMID: 21716274 RESULT

MeSH Terms

Interventions

Clopidogrel

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• International Clinical Development Study Director

  Sanofi

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2010
• First Posted: May 14, 2010
• Study Start: April 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: December 15, 2011

Record last verified: 2011-12

Locations

DE (1)