Clinical trial NCT01503658: Clinical Trial to Evaluate the Influence of Genotype on the Pharmacokinetics/Pharmacodynamics of Clopidogrel
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influence of Genotype of Drug Metabolizing Enzyme or Transporter on the Pharmacokinetics/Pharmacodynamics of Clopidogrel
Influence of Aspirin on the Pharmacokinetics/Pharmacodynamics of Clopidogrel
Keywords: Clopidogrel,
Aspirin,
Pharmacogenomics
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2012-01-04
Enrollment: 18
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics of Clopidogrel
timeFrame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h postdose on Day 1, Day 15 and Day 29
measure: Pharmacodynamics of clopidogrel
timeFrame: Predose and 4, 24 h postdose on Day 1, Day 15 and Day 29
Secondary outcomes:
measure: mRNA/microRNA/endogenous metabolite
timeFrame: predose on Day 1, Day 8, Day 15, Day 22 and Day 29
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital Clinical Trials Center
Study officials:
affiliation: Seoul National University Hospital
name: In-Jin Jang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oh J, Shin D, Lim KS, Lee S, Jung KH, Chu K, Hong KS, Shin KH, Cho JY, Yoon SH, Ji SC, Yu KS, Lee H, Jang IJ. Aspirin decreases systemic exposure to clopidogrel through modulation of P-glycoprotein but does not alter its antithrombotic activity. Clin Pharmacol Ther. 2014 Jun;95(6):608-16. doi: 10.1038/clpt.2014.49. Epub 2014 Feb 24.