An Interaction Study to Evaluate the Effect of Esomeprazole/Acetylsalicylic Acid on the Metabolism and Effect of Clopidogrel

Study Overview
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Brief Summary
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The primary purpose of this study is to assess whether esomeprazole 20 mg/Acetyl Salicylic Acid (ASA) 81 mg affect the metabolism of clopidogrel.

Official Title
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An Open-label, Randomized, Single-center, 2-way Cross-over Interaction Study, Evaluating the Effect of Esomeprazole 20 mg/Acetylsalicylic Acid 81 mg on the Pharmacodynamics and the Pharmacokinetics of Clopidogrel on Days 1 and 9 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Clopidogrel
* Drug: Esomeprazole/ASA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male (aged between 18 and 45 years inclusive) or female (aged between 18 and 55 years inclusive) healthy volunteers Female healthy volunteers must be of non-childbearing potential or be of childbearing potential, be non-lactating and have a negative pregnancy test during the pre-entry visit and be using 1 clinically accepted method of contraception Have a body mass index between 19 and 30 kg/m2 inclusive No clinically significant abnormal findings at the physical examination as judged by the investigator Exclusion Criteria: Any clinically significant abnormalities in laboratory screening results as judged by investigator Platelet count <150 x 10^9/L on Day -1 or any other conditions that would increase the risk of bleeding Previous bone marrow transplant Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG

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>Treatment A (Clopidogrel 9 days), at least 14 days wash-out, Treatment B (Clopidogrel 4 days followed by Clopidogrel + Esomeprazole/ASA 5 days) | Drug: Clopidogrel<br>* Clopidogrel<br>Drug: Esomeprazole/ASA<br>* 20 mg/81 mg once daily for five days (Day 5-9)<br>* Other names: Axanum;|
| Experimental: 2<br>Treatment B (Clopidogrel 4 days followed by Clopidogrel + Esomeprazole/ASA 5 days), at least 14 days wash-out, Treatment A (Clopidogrel 9 days) | Drug: Clopidogrel<br>* Clopidogrel<br>Drug: Esomeprazole/ASA<br>* 20 mg/81 mg once daily for five days (Day 5-9)<br>* Other names: Axanum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline |  | Pharmacodynamic sampling will be done before treatment period 1. | 
| The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline |  | Pharmacodynamic sampling will be done after treatment period 1 | 
| The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline |  | Pharmacodynamic sampling will be done before treatment period 2. | 
| The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline |  | Pharmacodynamic sampling will be done after treatment period 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacokinetics of the active metabolite of clopidogrel by assessing Area Under Curve (AUC) and Cmax.after 9 days of clopidogrel treatment |  | Pharmacokinetic sampling will be done at the end of treatment period 1 and 2 (Day 9). | 
| The safety and tolerability of clopidogrel alone and in combination with esomeprazole/ acetylsalicylic acid |  | Safety will be monitored continuously. Adverse events will be collected from the first administration of Investigational Product (IP) throughout the study until the follow-up visit (on average) 7-10 days after last dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phase 1, cross-over, drug-drug Interaction, esomeprazole, acetylsalicylic acid, clopidogrel, healthy volunteers, cardiovascular disease, patients with acid associated gastrointestinal symptoms