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

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

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

Study Overview

• Status: Completed
• Conditions: DRUG REACTIONS
• Intervention / Treatment: Drug: Aspirin+Clopidogrel/Digoxin(oral); Drug: Aspirin+Clopidogrel/Digoxin(IV)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: In-Jin Jang, MD, SNUH

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 15, 2013
• First Submitted That Met QC Criteria: January 22, 2013
• First Posted (Estimate): January 25, 2013

Study Record Updates

• Last Update Posted (Estimate): June 10, 2014
• Last Update Submitted That Met QC Criteria: June 8, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protective Agents; Cardiotonic Agents; Aspirin; Digoxin; Clopidogrel
• Other Study ID Numbers: PGX_Clopidogrel_002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No