Effect of Activated Charcoal on Rivaroxaban Pharmacokinetics in Healthy Subjects (RICHAR)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: rivaroxaban; Drug: rivaroxaban and 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: 18 years to 40 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 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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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; rivaroxaban 40 mg/day (1 day); Drug: rivaroxaban and activated charcoal; rivaroxaban 40 mg/day (1 day) and 50 g of activated charcoal 2 or 5 or 8 hours after rivaroxaban administration (1 day)
Experimental: Arm B; . 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; rivaroxaban 40 mg/day (1 day); Drug: rivaroxaban and activated charcoal; rivaroxaban 40 mg/day (1 day) and 50 g of activated charcoal 2 or 5 or 8 hours after rivaroxaban administration (1 day)
Experimental: Arm C; . 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; rivaroxaban 40 mg/day (1 day); Drug: rivaroxaban and activated charcoal; rivaroxaban 40 mg/day (1 day) and 50 g of activated charcoal 2 or 5 or 8 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	H0.5, H0.75, H1, H1.5, H2, H2.5, H3, H4, H5, H6, H8, H10, H12, H14, H18 and H24 after rivaroxaban administration

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Publications and helpful links

General Publications

• Ollier E, Hodin S, Lanoiselee J, Escal J, Accassat S, De Magalhaes E, Basset T, Bertoletti L, Mismetti P, Delavenne X. Effect of Activated Charcoal on Rivaroxaban Complex Absorption. Clin Pharmacokinet. 2017 Jul;56(7):793-801. doi: 10.1007/s40262-016-0485-1.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: January 14, 2016
• First Submitted That Met QC Criteria: January 14, 2016
• First Posted (Estimate): January 18, 2016

Study Record Updates

• Last Update Posted (Estimate): May 25, 2016
• Last Update Submitted That Met QC Criteria: May 24, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Rivaroxaban, pharmacokinetics, activated charcoal, poisoning
• 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: 1508030; 2015-001839-21 (EudraCT Number); 140096A-21 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

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