Switching Study From Warfarin to Rivaroxaban

Bayer

Status and phase: Completed; Phase 1

Conditions: Venous Thrombosis

Treatments: Drug: Vitamin K (Konakion); Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Warfarin (Coumadin); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01507051

10849

2008-005540-16 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 96 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

96 participants in 3 patient groups, including a placebo group

Warfarin followed by Rivaroxaban (Xarelto, BAY59-7939)

Experimental group

Description:

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

Treatment:

Drug: Vitamin K (Konakion)

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Drug: Warfarin (Coumadin)

Warfarin followed by Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Vitamin K (Konakion)

Drug: Warfarin (Coumadin)

Drug: Placebo

Rivaroxaban (Xarelto, BAY59-7939)

Active Comparator group

Description:

Days 0 to 3: 20 mg rivaroxaban once daily

Treatment:

Drug: Rivaroxaban (Xarelto, BAY59-7939)