Clinical Trial to Evaluate the Influence of Genotype and DDIs of Aspirin on the PK/PD of Clopidogrel and PK of Digoxin

Study Overview
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Brief Summary
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Clinical trial to evaluate the influence of multiple aspirin administration on PK and PD of co-administered drugs

Detailed Description
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Clinical trial to evaluate the influence of genotype of drug metabolizing enzyme or transporter and drug-drug interactions of aspirin co-administration on the pharmacokinetics / pharmacodynamics of clopidogrel and pharmacokinetics of digoxin in healthy volunteers

Official Title
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Clinical Trial to Evaluate the Influence of Genotype of Drug Metabolizing Enzyme or Transporter and Drug-drug Interactions of Aspirin Co-administration on the PK/PD of Clopidogrel and PK of Digoxin in Healthy Volunteers

Conditions
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DRUG REACTIONS

Intervention / Treatment
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* Drug: Aspirin+Clopidogrel/Digoxin(oral)
* Drug: Aspirin+Clopidogrel/Digoxin(IV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 20 - 45 years. 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). 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: Presence or history of hypersensitivity or allergic reactions to drugs including investigational product (clopidogrel, digoxin or aspirin) Clinically relevant abnormal medical history that could interfere with the objectives of the study. 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. 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. A subject whose SBP is over 160 mmHg or below 90 mmHg and DBP is over 100 mmHg or below 50 mmHg. Clinically significant abnormal findings of ECG during screening test. Presence or history of drug abuse or positive result in urine drug screening test. Participation in other clinical trial within 2 months before first dose. Use of CYP inducer (ex. rifampin) within 4 weeks before first dose. Use of a prescription medicine, herbal medicine within 2 weeks or over-the-counter medication or vitamin substances within 1 week before first dose. Use of grapefruit juice within 1 week before first dose. Blood donation during 2 months or apheresis during 1 month before the study. Use of alcohol over 21 units/weeks Smoking of more than 10 cigarettes/days within 3 months before first dose. 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin+Clopidogrel/Digoxin(oral)<br>Aspirin: Day 1   Day 59( 65; till the EGC) Clopidogrel: Day -3, 26, 54 Digoxin: Day -2, 27, 55 | Drug: Aspirin+Clopidogrel/Digoxin(oral)<br>* oral administration of digoxin<br>* Other names: Digoxin;|
| Experimental: Aspirin+Clopidogrel/Digoxin(IV)<br>Aspirin: Day 1   Day 59( 65; till the EGC) Clopidogrel: Day -3, 26, 54 Digoxin: Day -2, 27, 55 | Drug: Aspirin+Clopidogrel/Digoxin(IV)<br>* intravenous administration of digoxin<br>* Other names: Digoxin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC and Cmax of Clopidogrel and Digoxin | (Clopidogrel)Predose and 10, 20, 30, 40, 50 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h postdose on Week 0, 4, 8 (Digoxin) Predose and 10, 20, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 h postdose on Week 0, 4, 8 | pre- and post dose of Clopidogrel, Digoxin administration |