An Open-label, Randomized, 4-treatment, 3-period, Crossover Interaction Study, Evaluating the Effect of Esomeprazole 40 mg, Omeprazole 80 mg or Lansoprazole 60 mg on the Pharmacodynamics and the Pharmacokinetics of Clopidogrel in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 149
- Locations
- 1
- Primary Endpoint
- Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the inhibition of platelet aggregation (mIPA).
Study Overview
Brief Summary
The aim of this study is to determine if there is a pharmacological interaction between clopidogrel and different types of proton pump inhibitors (PPIs), and if the extent of this possible interaction would change over time.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy males within the age of 18-45 years and females within the age of 18-55 years with suitable veins for cannulation or repeated vein puncture. Females must be of non-childbearing potential.
- •Weight of 50-95kg, inclusive, and a BMI between 19-30 kg/m2, inclusive.
- •No clinically significant abnormal findings as judged by the Investigator on enrollment physical exam.
Exclusion Criteria
- •History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in study.
- •History or presence of gastrointestinal e.g. GI ulcer, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
- •Any clinically significant illness within 4 weeks of the first administration of investigational product. Any medical/surgical procedure or trauma within 3 months of the treatment period; scheduled surgery, including dental surgery within 2 weeks.
Arms & Interventions
1
lansoprazole 60 mg + clopidogrel 300 mg/ 75 mg
Intervention: clopidogrel (Drug)
1
lansoprazole 60 mg + clopidogrel 300 mg/ 75 mg
Intervention: lansoprazole (Drug)
2
omeprazole 80 mg + clopidogrel 300/75 mg
Intervention: omeprazole (Drug)
2
omeprazole 80 mg + clopidogrel 300/75 mg
Intervention: clopidogrel (Drug)
3
esomeprazole 40 mg + clopidogrel 300/75 mg
Intervention: esomeprazole (Drug)
3
esomeprazole 40 mg + clopidogrel 300/75 mg
Intervention: clopidogrel (Drug)
4
clopidogrel 300/75 mg alone
Intervention: clopidogrel (Drug)
Outcomes
Primary Outcomes
Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the inhibition of platelet aggregation (mIPA).
Time Frame: Day 30
Secondary Outcomes
- Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the AUC, AUC 0-t and Cmax after the loading dose of clopidogrel (Day 1) and AUC 0-t, ss and Css, max.(Days 5,14, 29)
- Evaluate the safety and tolerability of clopidogrel given concomittantly with esomeprazole, omeprazole or lansoprazole by assessment of adverse events and calculation of change from baseline for clinical laboratory tests, vital signs and pECG.(Every in-house day)