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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Activated charcoal

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Saint-etienne, France, 42000
    • CHU de Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 ...)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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; rivaroxaban 40 mg/day (1 day).; Drug: Activated charcoal; Activated charcoal 2 hours after rivaroxaban administration (1 day).
Experimental: Arm B; 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; rivaroxaban 40 mg/day (1 day).; Drug: Activated charcoal; Activated charcoal 2 hours after rivaroxaban administration (1 day).
Experimental: Arm C; 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; rivaroxaban 40 mg/day (1 day).; Drug: Activated charcoal; Activated charcoal 2 hours after rivaroxaban administration (1 day).
Experimental: Arm D; 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; rivaroxaban 40 mg/day (1 day).; Drug: Activated charcoal; Activated charcoal 2 hours after rivaroxaban administration (1 day).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2022
• Primary Completion (Actual): September 26, 2022
• Study Completion (Actual): November 4, 2022

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 21, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): December 5, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Poisoning; Rivaroxaban,; Activated charcoal
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Antidotes; Rivaroxaban; Charcoal
• Other Study ID Numbers: 18CH050; 2019-004425-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No