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

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ClinicalTrials.gov Identifier: NCT01400646
Recruitment Status : Completed
First Posted : July 22, 2011
Last Update Posted : January 24, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Rivaroxaban Drug: Warfarin Drug: Vitamin K Phase 1

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Non-Randomized, Sequential Two-Treatment Period Study to Explore the Pharmacodynamic Changes When Transitioning From Rivaroxaban to Warfarin
Study Start Date : October 2011
Primary Completion Date : May 2012
Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners
U.S. FDA Resources

Arms and Interventions

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: 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).
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: 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 2).


Outcome Measures

Primary Outcome Measures :
  1. Prothrombin time (PT) [ Time Frame: From Day 1 up to Day 9 ]
  2. International Ratio (INR) [ Time Frame: From Day 1 up to Day 9 ]

Secondary Outcome Measures :
  1. Plasma concentrations of Rivaroxaban [ Time Frame: Up to Day 9 ]
  2. Plasma concentrations of Warfarin [ Time Frame: Up to Day 12 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01400646


Locations
Belgium
Merksem, Belgium
Sponsors and Collaborators
Janssen Research & Development, LLC
Bayer
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01400646     History of Changes
Obsolete Identifiers: NCT01510925
Other Study ID Numbers: CR018664
RIVAROXAFL1004 ( Other Identifier: Janssen Research & Development )
2011-002890-46 ( EudraCT Number )
First Posted: July 22, 2011    Key Record Dates
Last Update Posted: January 24, 2017
Last Verified: January 2017

Keywords provided by Janssen Research & Development, LLC:
Rivaroxaban
JNJ-39039039
BAY59-7939
Warfarin
Transition

Additional relevant MeSH terms:
Vitamins
Vitamin K
Warfarin
Rivaroxaban
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifibrinolytic Agents
Fibrin Modulating Agents
Hemostatics
Coagulants