A Study to Explore the Pharmacodynamic Changes When Transitioning From Rivaroxaban to Warfarin in Healthy Volunteers

January 23, 2017 updated by: Janssen Research & Development, LLC

An Open-Label, Non-Randomized, Sequential Two-Treatment Period Study to Explore the Pharmacodynamic Changes When Transitioning From Rivaroxaban to Warfarin

The purpose of this study is to explore the pharmacodynamic (what the drug does to the body) changes when transitioning from rivaroxaban 20 mg once daily to warfarin dosed to a therapeutic level as measured by the International Normalized Ratio (INR) range of 2.0 to 3.0 in healthy volunteers. In addition, the pharmacokinetics (what the body does to the drug), safety and tolerability of rivaroxaban during the transition to warfarin will be investigated. The INR is obtained from a blood test, and is a measure for the clotting tendency of the blood used for safe and adequate dosing of warfarin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a single-center, open-label (study staff and healthy volunteers will know the identity of treatment assigned), sequential 2-treatment period study in healthy adult volunteers to explore the pharmacodynamic changes (changes drugs have on the body), specifically in regard to blood coagulation (blood clotting) when healthy volunteers take oral (by mouth) rivaroxaban followed by warfarin. Treatment Period 1: Rivaroxaban 20 mg/day for 5 days then Rivaoxaban 20 mg/day + Warfarin 10 mg/day for 2-4 days then warfarin 0-15 mg/day for 4 days. Treatment Period 2: Warfarin 10 mg/day for 2-4 days, then 0-15 mg/day for 4 days. Treatment periods 1 and 2 will be separated by a washout period of at least 14 days. In Treatment Periods 1 and 2, the dose of warfarin may be adjusted as specified by the protocol and the last dose of warfarin in each Treatment period will be followed by a single dose of Vitamin K. The approximate total study length for healthy adult volunteers enrolled is approximately 72 days (includes a 28-day Screening Period, a 30-day Open-label Treatment Phase, which includes the 7 days for a follow-up visit, and at least a 14-day washout between treatment periods).

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Volunteers must agree to provide a blood sample for pharmacogenomic testing and must have less than 3 of the variant CYP2C9 and VKORC1 gene alleles associated with increased warfarin sensitivity if their genetic status regarding these alleles is not previously known
  • Have coagulation test results (INR, PT, and activated partial thromboplastin time (aPTT) within clinically acceptable limits, blood pressure (after the volunteer is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and between 50 and 90 mmHg diastolic
  • Have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive), and body weight of not less than 50 kg
  • Be a Non-smoker (Volunteers may not use nicotine-containing products within 3 months prior to study drug administration

Exclusion Criteria:

  • Have a history or current clinically significant medical illness, including (but not limited to) of intracranial tumor or aneurysm
  • Have history of gastrointestinal disease (e.g., Crohn's disease) which could result in impaired absorption of the study drugs or history of clinically significant hemoptysis, excessive bruising, bleeding from nose or gums or known disorders with increased bleeding risk (e.g., acute gastritis, acute peptic ulcer) or history of any bleeding diathesis. Concomitant use (also within the last 2 weeks before start of the study) of drugs that influenced the coagulation system, e.g., antiplatelet drugs (e.g., acetylsalicylic acid, ticlopidine and clopidogrel
  • abciximab, tirofiban and integrelin) or other anticoagulants (antithrombins, unfractionated heparins, low molecular weight heparins and hirudin, coumadin-type anticoagulants phenprocoumon, warfarin, dabigatran, probenecide)
  • Use of medications known to affect the metabolic pathways (CYP3A4, or P-gp) within 14 days of study admission

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rivaroxaban + Warfarin Concomitant Therapy Phase
Rivaroxaban monotherapy 20 mg/day for 5 days followed by Rivaroxaban 20 mg/day + Warfarin. 10 mg/day for >= 2 to <= 4 days concomitant therapy, then Warfarin monotherapy 0-15 mg/day for 4 days (Treatment Period 1). A 14-day washout period will separate Treatment Periods 1 and 2.
Drug: Rivaroxaban
Type=exact number, unit=mg, number=20, form=tablet, route=oral use. One tablet once daily for 5 days (Treatment Period 1, Days 1-7).
Drug: Warfarin
Type=exact number, unit mg, number=10, form=tablet , route=oral use. One tablet for 2-4 days (Treatment Period 1, Day 6 up to Day 11).
Drug: Vitamin K
Type=exact number, unit=mg, number=1, form=oral solution, route=oral use. 1 mg dose for 1 day (Treatment Period 1, Day 12).
Drug: Vitamin K
Type=exact number, unit=mg, number=5, form=oral solution, route=oral use. 5 mg dose for 1 day (Treatment Period 2, Day 7).
Drug: Warfarin
Type-exact number, unit=mg, number=10, form=tablet, route=oral use. Tablet(s) administered once daily for 2-4 days (Treatment Period 2, Day 1 up to Day 6)
Drug: Warfarin
Type=range, unit=mg, number=0-15, form=tablet, route=oral use. Tablet(s) taken once daily for up to 4 days after Warfarin 10 mg administered as monotherapy for 2-4 days (Treatment Period 1).
Drug: Warfarin
Type=range, unit=mg, number=0-15, form=tablet, route=oral use. Tablet(s) taken once daily for up to 4 days after Warfarin 10 mg administered as monotherapy for 2-4 days (Treatment Period 2).
Experimental: Warfarin Monotherapy Phase
Warfarin monotherapy 10 mg/day for >=2 to <=4 days, then Warfarin 0-15 mg/day for 4 days (Treatment Period 2). A 14-day washout period will separate Treatment Periods 1 and 2.
Drug: Warfarin
Type=exact number, unit mg, number=10, form=tablet , route=oral use. One tablet for 2-4 days (Treatment Period 1, Day 6 up to Day 11).
Drug: Vitamin K
Type=exact number, unit=mg, number=1, form=oral solution, route=oral use. 1 mg dose for 1 day (Treatment Period 1, Day 12).
Drug: Vitamin K
Type=exact number, unit=mg, number=5, form=oral solution, route=oral use. 5 mg dose for 1 day (Treatment Period 2, Day 7).
Drug: Warfarin
Type-exact number, unit=mg, number=10, form=tablet, route=oral use. Tablet(s) administered once daily for 2-4 days (Treatment Period 2, Day 1 up to Day 6)
Drug: Warfarin
Type=range, unit=mg, number=0-15, form=tablet, route=oral use. Tablet(s) taken once daily for up to 4 days after Warfarin 10 mg administered as monotherapy for 2-4 days (Treatment Period 1).
Drug: Warfarin
Type=range, unit=mg, number=0-15, form=tablet, route=oral use. Tablet(s) taken once daily for up to 4 days after Warfarin 10 mg administered as monotherapy for 2-4 days (Treatment Period 2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Prothrombin time (PT)
Time Frame: From Day 1 up to Day 9
From Day 1 up to Day 9
International Ratio (INR)
Time Frame: From Day 1 up to Day 9
From Day 1 up to Day 9

Secondary Outcome Measures

Outcome Measure
Time Frame
Plasma concentrations of Rivaroxaban
Time Frame: Up to Day 9
Up to Day 9
Plasma concentrations of Warfarin
Time Frame: Up to Day 12
Up to Day 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen Research & Development, LLC

Collaborators

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

July 21, 2011

First Submitted That Met QC Criteria

July 21, 2011

First Posted (Estimate)

July 22, 2011

Study Record Updates

Last Update Posted (Estimate)

January 24, 2017

Last Update Submitted That Met QC Criteria

January 23, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR018664
  • RIVAROXAFL1004 (Other Identifier: Janssen Research & Development)
  • 2011-002890-46 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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