Study Evaluating Effect of Esomeprazole, Omeprazole or Lansoprazole on the Pharmacodynamics (PD) and Pharmacokinetics (PK) of Clopidogrel

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: lansoprazole
* Drug: omeprazole
* Drug: esomeprazole
* Drug: clopidogrel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>lansoprazole 60 mg + clopidogrel 300 mg/ 75 mg | Drug: lansoprazole<br>* 60 mg (2x30-mg capsule), once daily<br>Drug: clopidogrel<br>* 300 mg loading dose on Day 1 then 75 mg daily for 28 days<br>|
| Experimental: 2<br>omeprazole 80 mg + clopidogrel 300/75 mg | Drug: omeprazole<br>* 80 mg (2x40-mg capsule), once daily<br>Drug: clopidogrel<br>* 300 mg loading dose on Day 1 then 75 mg daily for 28 days<br>|
| Experimental: 3<br>esomeprazole 40 mg + clopidogrel 300/75 mg | Drug: esomeprazole<br>* 40 mg (1x40-mg capsule), once daily<br>Drug: clopidogrel<br>* 300 mg loading dose on Day 1 then 75 mg daily for 28 days<br>|
| Experimental: 4<br>clopidogrel 300/75 mg alone | Drug: clopidogrel<br>* 300 mg loading dose on Day 1 then 75 mg daily for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). |  | Baseline | 
| 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). |  | Day 2 | 
| 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). |  | Day 6 | 
| 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). |  | Day 15 | 
| 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). |  | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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open label, randomized, 4-treatment, 3-period, crossover, interaction study, Safety, tolerability, pharmacokinetics, pharmacodynamics