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

Condition(s) targeted: Healthy

Intervention: Warfarin (Drug); Rivaroxaban (Drug); Warfarin (Drug); Vitamin K (Drug); Vitamin K (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Official(s) and/or principal investigator(s):
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Overall contact:
Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

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.

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

Study design: Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Prothrombin time (PT)

International Ratio (INR)

Secondary outcome:

Plasma concentrations of Rivaroxaban

Plasma concentrations of Warfarin

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 (Tx) Period 1: Rivaroxaban (Riva) 20 mg/day for 5 days then Riva 20 mg/day + Warfarin 5 mg/day for 2-4 days then warfarin 0-15 mg/day for 4 days. Tx Period 2: Warfarin 5 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 Tx Periods 1 and 2, the dose of warfarin will be adjusted as specified by the protocol and the last dose of warfarin in each Tx period will be followed by a single dose of Vitamin K.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

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

- Have coagulation test results (INR, PT, and activated partial thromboplasin time

(aPTT) within clinically acceptable limits, blood pressure (after the volunteer is sitting for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 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

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

Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

Merksem, Belgium; Recruiting

To learn how to participate in this trial please click here.

Starting date: October 2011
Last updated: December 2, 2011