A Study to Explore the Pharmacodynamic Changes When Transitioning From Rivaroxaban to Warfarin in Healthy Volunteers
Information source: Janssen Research & Development, LLC
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Rivaroxaban (Drug); Warfarin (Drug); Vitamin K (Drug); Vitamin K (Drug); Warfarin (Drug); Warfarin (Drug); Warfarin (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Janssen Research & Development, LLC Official(s) and/or principal investigator(s): Janssen Research & Development, LLC Clinical Trial, Study Director, Affiliation: Janssen Research & Development, LLC
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.
Clinical Details
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 RivaroxabanPlasma 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 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
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 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
Locations and Contacts
Merksem, Belgium
Additional Information
Starting date: October 2011
Last updated: March 1, 2013
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