Influence of Aspirin on the Pharmacokinetics/Pharmacodynamics of Clopidogrel, Influence of Genotype of Drug Metabolizing Enzyme or Transporter on the Pharmacokinetics/Pharmacodynamics of Clopidogrel
Conditions
Keywords
Clopidogrel,, Aspirin,, Pharmacogenomics
Brief summary
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
Interventions
Clopidogrel 75 mg, Aspirin 100 mg
Sponsors
Seoul National University Hospital
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics 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 | Plasma concentration of clopidogrel and active metabolite of clopidogrel |
| Pharmacodynamics of clopidogrel | Predose and 4, 24 h postdose on Day 1, Day 15 and Day 29 | Relative inhibition of platelet aggregation by aggregometer or VerifyNow |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mRNA/microRNA/endogenous metabolite | predose on Day 1, Day 8, Day 15, Day 22 and Day 29 | mRNA of PON1 and CYP2C19, CYP3A5, MDR1 microRNA endogenous metabolite |
Countries
South Korea
Outcome results
None listed