Non Inferiority Study of a Reduced Dose of Activated Charcoal on Rivaroxaban Pharmacokinetics.

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. A recent study, in healthy subjects, shows that activated charcoal can reduce significantly exposition to rivaroxaban. However, no results are available on the minimal dose of activated charcoal necessary in rivaroxaban poisoning. The objective of this study is to evaluate the effect of 4 dosing regimen 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 with 50g, 24g, 12g and 6g of activated charcoal administrated 3 hours after rivaroxaban intake.

Official Title
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Non Inferiority Study of a Reduced Dose of Activated Charcoal on Rivaroxaban Pharmacokinetics.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: 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 biologic consent form Men aged between 18 and 40 years Weight between 55 and 92 kilogram normal clinical exam normal biological exam Exclusion Criteria: Contra-indication to rivaroxaban Contra-indication to activated charcoal With a history of hemorrhagic disease Smoker Organic lesion likely to bleed Severe liver disease Severe kidney failure Gastroduodenal ulcers Any medication taken during the week prior to the start of the study Consumption of grapefruit juice Routine ingestion of excessive amounts of coffee, tea, chocolate and/or caffeinated beverages Practice of violent sports Fructose intolerance Glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency syndrome Notable medical history (cardiovascular pathology, pulmonary, neurology ...)

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

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Period  rivaroxaban and 6 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 12 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 50 milligram of activated charcoal  Washout period (6 days) | Drug: Rivaroxaban<br>* rivaroxaban 40 mg/day (1 day).<br>Drug: Activated charcoal<br>* Activated charcoal 2 hours after rivaroxaban administration (1 day).<br>|
| Experimental: Arm B<br>Period  rivaroxaban and 12 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 6 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 24 milligram of activated charcoal  Washout period (6 days) | Drug: Rivaroxaban<br>* rivaroxaban 40 mg/day (1 day).<br>Drug: Activated charcoal<br>* Activated charcoal 2 hours after rivaroxaban administration (1 day).<br>|
| Experimental: Arm C<br>Period  rivaroxaban and 50 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 24 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 6 milligram of activated charcoal  Washout period (6 days) | Drug: Rivaroxaban<br>* rivaroxaban 40 mg/day (1 day).<br>Drug: Activated charcoal<br>* Activated charcoal 2 hours after rivaroxaban administration (1 day).<br>|
| Experimental: Arm D<br>Period  rivaroxaban and 24 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 50 milligram of activated charcoal  Washout period (6 days) Period  rivaroxaban and 12 milligram of activated charcoal  Washout period (6 days) | Drug: Rivaroxaban<br>* rivaroxaban 40 mg/day (1 day).<br>Drug: Activated charcoal<br>* Activated charcoal 2 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 | 1, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 24 hours after rivaroxaban administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Analysis adverse events related to the administration of treatment. | 24 hour after rivaroxaban administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Poisoning, Rivaroxaban,, Activated charcoal, Pharmacokinetics