Non Inferiority Study of a Reduced Dose of Activated Charcoal on Rivaroxaban Pharmacokinetics. (RICHAR2)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Activated charcoal; Drug: Rivaroxaban

Study type: Interventional

Funder types: Other

Identifiers

NCT04767776

2019-004425-25 (EudraCT Number)

18CH050

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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 ...)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

---

12 participants in 4 patient groups

Arm A

Experimental group

Description:

* 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)

Treatment:

Drug: Activated charcoal

Drug: Rivaroxaban

Arm B

Experimental group

Description:

* 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)

Treatment:

Drug: Activated charcoal

Drug: Rivaroxaban

Arm C

Experimental group

Description:

* 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)

Treatment:

Drug: Activated charcoal

Drug: Rivaroxaban

Arm D

Experimental group

Description:

* 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)

Treatment:

Drug: Activated charcoal

Drug: Rivaroxaban