Effect of Inhibitors of the Proton Pump on Intestinal Transporters

Study Overview
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Brief Summary
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Dabigatran etexilate is a novel oral anticoagulant. It is indicated in venous thromboembolic prevention in orthopedic surgery and has recently shown greater efficiency and tolerance as anticoagulants in preventing thromboembolism in atrial fibrillation. However, it increases the risk of gastrointestinal bleeding compared to standard treatment (AVK) [3]. In these circumstances the risk / benefit of dabigatran could be improved by combining it with gastric protectors such as inhibitor drugs proton pump (IPP). Investigators want to evaluate the pharmacokinetic and pharmacodynamic effects of co-administration of these two IPP (omeprazole, rabeprazole) with dabigatran in healthy subjects.

Official Title
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Effect of Inhibitors of the Proton Pump on Intestinal Transporters and Their Impact on the Pharmacokinetics of Dabigatran - Mechanistic and Clinical Approach -BIPP Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran
* Drug: Rabeprazole and Dabigatran
* Drug: Omeprazole and Dabigatran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: weight between 60 and 85 kg normal clinical exam normal biological exam Exclusion Criteria: hypersensitivity to dabigatran or any of its excipients hypersensitivity to omeprazole or rabeprazole or any of its excipients previous history of hemorrhagic disease insufficiency liver severe kidney failure peptic ulcer Any drug taken during the week before the start of the study smoker Consumption of grapefruit juice practice of violent sport

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

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

Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Period  Dabigatran Washout period (at least 6 days) Period  Rabeprazole + Dabigatran Washout period (at least 6 days) Period  Omeprazole + Dabigatran | Drug: Dabigatran<br>* dabigatran etexilate 150 mg/day (1 day)<br>Drug: Rabeprazole and Dabigatran<br>* rabeprazole 20 mg / day for 5 days, then the 6th day concomitant rabeprazole 20 mg of dabigatran etexilate 150 mg;<br>Drug: Omeprazole and Dabigatran<br>* omeprazole 20 mg / day for 5 days, then the sixth day concomitant omeprazole 20 mg and 150 mg dabigatran etexilate<br>|
| Experimental: Arm B<br>Period Rabeprazole + Dabigatran  Washout period (at least 6 days) Period  Dabigatran Washout period (at least 6 days) Period  Omeprazole + Dabigatran | Drug: Dabigatran<br>* dabigatran etexilate 150 mg/day (1 day)<br>Drug: Rabeprazole and Dabigatran<br>* rabeprazole 20 mg / day for 5 days, then the 6th day concomitant rabeprazole 20 mg of dabigatran etexilate 150 mg;<br>Drug: Omeprazole and Dabigatran<br>* omeprazole 20 mg / day for 5 days, then the sixth day concomitant omeprazole 20 mg and 150 mg dabigatran etexilate<br>|
| Experimental: Arm C<br>Period  Rabeprazole + Dabigatran Period  Omeprazole + Dabigatran Period  Dabigatran | Drug: Dabigatran<br>* dabigatran etexilate 150 mg/day (1 day)<br>Drug: Rabeprazole and Dabigatran<br>* rabeprazole 20 mg / day for 5 days, then the 6th day concomitant rabeprazole 20 mg of dabigatran etexilate 150 mg;<br>Drug: Omeprazole and Dabigatran<br>* omeprazole 20 mg / day for 5 days, then the sixth day concomitant omeprazole 20 mg and 150 mg dabigatran etexilate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) from plasma concentrations of dabigatran | Area under the curve (AUC) from plasma concentrations of dabigatran | baseline after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 0.25 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 0.5 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 1 hour after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 1.5 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 2 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 3 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 6 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 8 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 12 hours after each dose of dabigatran etexilate. | 
| Area under the curve (AUC) from plasma concentrations of dabigatran |  | 24 hours after each dose of dabigatran etexilate. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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volunteers