Switching Study From Warfarin to Rivaroxaban

NCT ID: NCT01507051

Last Updated: 2015-02-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2009-11-30

Brief Summary

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The study objective is to investigate the pharmacodynamics (effects of a drug product) when switching the treatment from warfarin to rivaroxaban.

84 young, healthy subjects will participate; they will be treated following a randomized, parallel-group (Treatments A, B, and C), placebo-controlled (Treatment B), and single-blind (Treatments A and B) design.

The first two groups (A, B) will receive warfarin for approximately one week to adjust their blood coagulation values to a specific level, i.e. to maintain an INR (international normalized ratio) of 2.0 - 3.0. This range is commonly used for long-term anticoagulant treatment.

The first group (A) will receive rivaroxaban for four days, the second group (B) will take placebo. On the last day, all subjects in groups A and B will receive vitamin K to neutralize the effects of warfarin. The third group (C) will not undergo prior treatment with warfarin but will receive rivaroxaban for four days.

Detailed Description

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Conditions

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Venous Thrombosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

SINGLE

Participants

Study Groups

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Warfarin followed by Rivaroxaban (Xarelto, BAY59-7939)

Days -6 and -5: 10 mg warfarin once daily or lower depending on international normalized ratio (INR); Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin once daily depending on INR; Days 0 to 3: 20 mg rivaroxaban once daily; Day 5: 10 mg vitamin K once daily

Group Type EXPERIMENTAL

Warfarin (Coumadin)

Intervention Type DRUG

Days -6 and -5: 10 mg warfarin (Coumadin) once daily, dosage lower if the INR is already high on day -5; Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin (Coumadin) once daily, dosage depending on INR

Rivaroxaban (Xarelto, BAY59-7939)

Intervention Type DRUG

Days 0 to 3: 20 mg rivaroxaban once daily

Vitamin K (Konakion)

Intervention Type DRUG

Day 5: 10 mg vitamin K (Konakion) once daily

Warfarin followed by Placebo

Days -6 and -5: 10 mg warfarin once daily or lower depending on INR; Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin once daily depending on INR; Days 0 to 3: 1 tablet matching placebo once daily; Day 5: 10 mg vitamin K once daily

Group Type PLACEBO_COMPARATOR

Warfarin (Coumadin)

Intervention Type DRUG

Days -6 and -5: 10 mg warfarin (Coumadin) once daily, dosage lower if the INR is already high on day -5; Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin (Coumadin) once daily, dosage depending on INR

Placebo

Intervention Type DRUG

Days 0 to 3: 1 tablet placebo, identical to active tablet

Vitamin K (Konakion)

Intervention Type DRUG

Day 5: 10 mg vitamin K (Konakion) once daily

Rivaroxaban (Xarelto, BAY59-7939)

Days 0 to 3: 20 mg rivaroxaban once daily

Group Type ACTIVE_COMPARATOR

Rivaroxaban (Xarelto, BAY59-7939)

Intervention Type DRUG

Days 0 to 3: 20 mg rivaroxaban once daily

Interventions

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Warfarin (Coumadin)

Days -6 and -5: 10 mg warfarin (Coumadin) once daily, dosage lower if the INR is already high on day -5; Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin (Coumadin) once daily, dosage depending on INR

Intervention Type DRUG

Rivaroxaban (Xarelto, BAY59-7939)

Days 0 to 3: 20 mg rivaroxaban once daily

Intervention Type DRUG

Placebo

Days 0 to 3: 1 tablet placebo, identical to active tablet

Intervention Type DRUG

Vitamin K (Konakion)

Day 5: 10 mg vitamin K (Konakion) once daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 18 to 45 years of age;
* Normal body weight: BMI (body mass index) between 18 and 29 kg/m2;
* Pharmacogenetics: subjects who are homozygous for the wildtype allele 2C9\*1 and who are carriers of the C-allele at positions 6484 and 7566 of the VKORC1 (vitamin K epoxide reductase) gene, respectively

Exclusion Criteria

* Relevant deviation from the normal range in the clinical examination;
* Relevant deviation from the normal range in clinical chemistry, hematology or urinalysis;
* Resting heart rate in the awake subject below 45 BPM (beats per minute) or above 90 BPM;
* Systolic blood pressure below 100 mmHg or above 140 mmHg; and Diastolic blood pressure above 85 mmHg;
* Relevant pathological changes in the ECG (electrocardiogram) such as a second or third-degree AV block, prolongation of the QRS (QRS complex in ECG) complex over 120 msec or of the QT / QTc-interval over 450 msec (QT interval in ECG, QTc interval corrected for heart rate);
* Subject is tested to be HIV-1/2Ab, p24Ag, HbsAg or HCV-Ab positive;
* Known coagulation disorders (e.g. von Willebrand's disease, haemophiliac);
* Known disorders with increased bleeding risks (e.g. periodontosis, hemorrhoids, acute gastritis, peptic ulcer);
* Known sensitivity to common causes of bleeding (e.g. nasal);
* Recent or planned surgical or diagnostic procedures at the central nervous system (CNS) or eye;
* Subjects with hyperlipidemia (Coumadin / warfarin warning)
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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Cologne, North Rhine-Westphalia, Germany

Site Status

Mönchengladbach, North Rhine-Westphalia, Germany

Site Status

Countries

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Germany

References

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Kubitza D, Becka M, Muck W, Kratzschmar J. Pharmacodynamics and pharmacokinetics during the transition from warfarin to rivaroxaban: a randomized study in healthy subjects. Br J Clin Pharmacol. 2014 Aug;78(2):353-63. doi: 10.1111/bcp.12349.

Reference Type RESULT
PMID: 24528331 (View on PubMed)

Related Links

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http://www.clinicaltrialsregister.eu

Click here and search for results posted for EMA

Other Identifiers

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2008-005540-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

10849

Identifier Type: -

Identifier Source: org_study_id

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