Effect of Activated Charcoal on Rivaroxaban Pharmacokinetics in Healthy Subjects

Study Overview
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Brief Summary
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Rivaroxaban is a direct oral anticoagulant that target specifically activated factor X. Bleeding events related to rivaroxaban are the consequence of physiopathologic, pharmacokinetic issues or poisoning. Few results are available on the use of activated charcoal in rivaroxaban poisoning. Moreover, a recent study, in healthy subjects, shows that activated charcoal can reduce significantly exposition to apixaban (a direct oral anticoagulant of the same class). The objective of this study is to evaluate the effect of activated charcoal on rivaroxaban pharmacokinetics. It corresponds to a randomised open trial with an incomplete cross over design (3 occasions). It will enrol 12 healthy subjects. Four treatments modalities will be studied: rivaroxaban alone and rivaroxaban with activated charcoal administrated 2, 4 or 8 hours after rivaroxaban administration.

Official Title
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Effect of Activated Charcoal on Rivaroxaban Pharmacokinetics in Healthy Subjects : RICHAR Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: rivaroxaban
* Drug: rivaroxaban and activated charcoal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: affiliated or beneficiary of a social security category having signed the inform consent form having signed the genetic consent form BMI between 18.5 and 25 normal clinical exam normal biological exam Exclusion Criteria: contra-indication to rivaroxaban contra-indication to activated charcoal previous history of psychiatric disease, or antidepressant treatment, or convulsion, or hemorrhagic disease smoker Organic lesion likely to bleed severe liver disease severe kidney failure previous surgery within one month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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  rivaroxaban alone Washout period (at least 6 days) Period  rivaroxaban and activated charcoal 2 hours after rivaroxaban administration Washout period (at least 6 days) Period   rivaroxaban and activated charcoal 5 hours after rivaroxaban administration | Drug: rivaroxaban<br>* rivaroxaban 40 mg/day (1 day)<br>Drug: rivaroxaban and activated charcoal<br>* rivaroxaban 40 mg/day (1 day) and 50 g of activated charcoal 2 or 5 or 8 hours after rivaroxaban administration (1 day)<br>|
| Experimental: Arm B<br>. Period  rivaroxaban and activated charcoal 5 hours after rivaroxaban administration Washout period (at least 6 days) Period  rivaroxaban alone Washout period (at least 6 days) Period   rivaroxaban and activated charcoal 8 hours after rivaroxaban administration | Drug: rivaroxaban<br>* rivaroxaban 40 mg/day (1 day)<br>Drug: rivaroxaban and activated charcoal<br>* rivaroxaban 40 mg/day (1 day) and 50 g of activated charcoal 2 or 5 or 8 hours after rivaroxaban administration (1 day)<br>|
| Experimental: Arm C<br>. Period  rivaroxaban and activated charcoal 2 hours after rivaroxaban administration Washout period (at least 6 days) Period   rivaroxaban and activated charcoal 8 hours after rivaroxaban administration Washout period (at least 6 days) Period  rivaroxaban alone | Drug: rivaroxaban<br>* rivaroxaban 40 mg/day (1 day)<br>Drug: rivaroxaban and activated charcoal<br>* rivaroxaban 40 mg/day (1 day) and 50 g of activated charcoal 2 or 5 or 8 hours after rivaroxaban administration (1 day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma concentrations of rivaroxaban | rivaroxaban pharmacokinetics | H0.5, H0.75, H1, H1.5, H2, H2.5, H3, H4, H5, H6, H8, H10, H12, H14, H18 and H24 after rivaroxaban administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rivaroxaban, pharmacokinetics, activated charcoal, poisoning