A Study to Explore the Pharmacodynamic Changes When Transitioning From Rivaroxaban to Warfarin in Healthy Volunteers
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Healthy |
Drug: Rivaroxaban Drug: Warfarin Drug: Vitamin K |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: 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 |
- Prothrombin time (PT) [ Time Frame: From Day 1 up to Day 9 ] [ Designated as safety issue: No ]
- International Ratio (INR) [ Time Frame: From Day 1 up to Day 9 ] [ Designated as safety issue: No ]
- Plasma concentrations of Rivaroxaban [ Time Frame: Up to Day 9 ] [ Designated as safety issue: No ]
- Plasma concentrations of Warfarin [ Time Frame: Up to Day 12 ] [ Designated as safety issue: No ]
| Enrollment: | 46 |
| Study Start Date: | October 2011 |
| Study Completion Date: | May 2012 |
| Primary Completion Date: | May 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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).
|
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).
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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 More Information
No publications provided
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT01400646 History of Changes |
| Obsolete Identifiers: | NCT01510925 |
| Other Study ID Numbers: | CR018664, RIVAROXAFL1004, 2011-002890-46 |
| Study First Received: | July 21, 2011 |
| Last Updated: | March 1, 2013 |
| Health Authority: | Belgium: Belgium Federal Agency for Medicinal Products and Health Products |
Keywords provided by Janssen Research & Development, LLC:
|
Rivaroxaban JNJ-39039039 BAY59-7939 Warfarin Transition |
Additional relevant MeSH terms:
|
Vitamin K Vitamins Warfarin Micronutrients Growth Substances Physiological Effects of Drugs Pharmacologic Actions Antifibrinolytic Agents |
Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Hemostatics Coagulants Hematologic Agents Therapeutic Uses Anticoagulants |
ClinicalTrials.gov processed this record on May 21, 2013