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

NCT01400646 | Completed Phase 1

• 3 other identifiers: CR018664RIVAROXAFL10042011-002890-46
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Rivaroxaban; JNJ-39039039; BAY59-7939; Warfarin; Transition

Outcome Measures

Primary Outcomes (2)

• Prothrombin time (PT)

  From Day 1 up to Day 9

• International Ratio (INR)

  From Day 1 up to Day 9

Secondary Outcomes (2)

• Plasma concentrations of Rivaroxaban

  Up to Day 9

• Plasma concentrations of Warfarin

  Up to Day 12

Study Arms (2)

Rivaroxaban + Warfarin Concomitant Therapy Phase

EXPERIMENTAL

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; Drug: Warfarin; Drug: Vitamin K

Warfarin Monotherapy Phase

EXPERIMENTAL

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; Drug: Warfarin

Interventions

Rivaroxaban DRUG

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).

Rivaroxaban + Warfarin Concomitant Therapy Phase

Warfarin DRUG

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).

Rivaroxaban + Warfarin Concomitant Therapy Phase

Vitamin K DRUG

Type=exact number, unit=mg, number=1, form=oral solution, route=oral use. 1 mg dose for 1 day (Treatment Period 1, Day 12).

Rivaroxaban + Warfarin Concomitant Therapy Phase

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• Bayer: collaborator

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

Related Publications (1)

• Moore KT, Byra W, Vaidyanathan S, Natarajan J, Ariyawansa J, Salih H, Turner KC. Switching from rivaroxaban to warfarin: an open label pharmacodynamic study in healthy subjects. Br J Clin Pharmacol. 2015 Jun;79(6):907-17. doi: 10.1111/bcp.12559.

  PMID: 25475601 DERIVED

MeSH Terms

Interventions

Rivaroxaban; Warfarin; Vitamin K

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phytol; Diterpenes; Terpenes; Polycyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2011
• First Posted: July 22, 2011
• Study Start: October 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: January 24, 2017

Record last verified: 2017-01

Locations

BE (1)