Clinical Trial to Evaluate the Influence of Genotype on the Pharmacokinetics/Pharmacodynamics of Clopidogrel

Study Overview
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Brief Summary
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This study has an open-label, five-period, single-sequence design. The purpose of this study is as follows; Primary To evaluate the influence of genotype of drug metabolizing enzyme or transporter on the pharmacokinetics/pharmacodynamics of clopidogrel To evaluate the influence of aspirin on the pharmacokinetics/pharmacodynamics of clopidogrel Secondary To explore the representative biomarkers for the variable pharmacokinetics/pharmacodynamics of clopidogrel To evaluate the influence of genotype of drug metabolizing enzyme or transporter on the drug-drug interactions between aspirin and clopidogrel To explore the representative biomarkers for the drug-drug interactions between aspirin and clopidogrel

Official Title
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Clinical Trial to Evaluate the Influence of Genotype of Drug Metabolizing Enzyme or Transporter and Drug-drug Interactions on the Pharmacokinetics/Pharmacodynamics of Clopidogrel in Healthy Volunteers

Conditions
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Influence of Genotype of Drug Metabolizing Enzyme or Transporter on the Pharmacokinetics/Pharmacodynamics of Clopidogrel, Influence of Aspirin on the Pharmacokinetics/Pharmacodynamics of Clopidogrel

Intervention / Treatment
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* Drug: Clopidogrel+Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Healthy male subjects aged 20 - 45 years. 2. A body weight in the range of 50 kg (inclusive) - 90 kg (exclusive) and a body mass index (BMI) in the range 18.5 kg/m2 (inclusive) - 27 kg/m2 (inclusive). 3. Sufficient ability to understand the nature of the study and any hazards of participating in it. Provide written informed consent after being fully. informed about the study procedures. Exclusion Criteria: 1. Presence or history of hypersensitivity or allergic reactions to drugs including investigational product (clopidogrel or aspirin) 2. Clinically relevant abnormal medical history that could interfere with the objectives of the study. 3. A subject with history of gastrointestinal disease or surgery (except simple appendectomy or repair of hernia), which can influence the absorption of the study drug. 4. A subject whose lab test results are as follows; Platelet count or PT, aPTT < 0.9 x lower limit of reference range of > 1.1 x upper limit of reference range. 5. A subject whose SBP is over 160 mmHg or below 90 mmHg and DBP is over 100 mmHg or below 50 mmHg. 6. Presence or history of drug abuse or positive result in urine drug screening test. 7. Participation in other clinical trial within 2 months before first dose. 8. Use of CYP inducer (ex. rifampin) within 4 weeks before first dose. 9. Use of a prescription medicine, herbal medicine within 2 weeks or over-the-counter medication or vitamin substances within 1 week before first dose. 10.Use of grapefruit juice within 1 week before first dose. 11. Blood donation during 2 months or apheresis during 1 month before the study. 12. Use of alcohol over 21 units/weeks 13. Smoking of more than 10 cigarettes/days within 3 months before first dose. 14. Subject judged not eligible for study participation by investigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clopidogrel+Aspirin<br>Clopidogrel on Day 1, Aspirin on Day 2 - Day 14, Clopidogrel + Aspirin Day 15, Aspirin on Day 16 - Day 28, Clopidogrel + Aspirin Day 29 | Drug: Clopidogrel+Aspirin<br>* Clopidogrel 75 mg, Aspirin 100 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Clopidogrel | Plasma concentration of clopidogrel and active metabolite of clopidogrel | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h postdose on Day 1, Day 15 and Day 29 | 
| Pharmacodynamics of clopidogrel | Relative inhibition of platelet aggregation by aggregometer or VerifyNow | Predose and 4, 24 h postdose on Day 1, Day 15 and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mRNA/microRNA/endogenous metabolite | mRNA of PON1 and CYP2C19, CYP3A5, MDR1 microRNA endogenous metabolite | predose on Day 1, Day 8, Day 15, Day 22 and Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clopidogrel,, Aspirin,, Pharmacogenomics