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

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

This study has an open-label, five-period, single-sequence design. The purpose of this study is as follows;

1. 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

2. 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

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.