check_circleStudy Completed

Venous thrombosis

Bayer Identifier:

10849

ClinicalTrials.gov Identifier:

NCT01507051

EudraCT Number:

2008-005540-16

EU CT Number:

Not Available
Switching study from warfarin to rivaroxaban

Trial purpose

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.

Key Participants Requirements

Sex

Male

Age

18 - 45 Years
  • - 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

  • - 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 summary

Enrollment Goal
96
Trial Dates
November 2008 - November 2009
Phase
Phase 1
Could I Receive a placebo
Yes
Products
Xarelto (Rivaroxaban, BAY59-7939)
Accepts Healthy Volunteer
Yes

Where to participate

StatusInstitutionLocation
Completed
MEDA Manufacturing GmbH, ClinPharmCologneKöln, 51063, Germany
Completed
CRS Clinical-Research-Services Mönchengladbach GmbHMönchengladbach, 41061, Germany

Primary Outcome

  • Emax (maximum effect) on Prothrombin Time (PT) (coagulation test)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax,BA (baseline adjusted maximum effect) on Prothrombin time (coagulation test)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of Prothrombin time (coagulation test)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUCBA(0-tn) (baseline adjusted area under the measurement versus time curve from time 0 to the last data point) of Prothrombin time (coagulation test)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax on PT (measured as INR=International Normalized Ratio)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) for PT (measured as INR=International Normalized Ratio)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax on Factor Xa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the inverse measurement versus time curve from time 0 to the last data point) of Factor Xa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on anti-Factor Xa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of anti-Factor Xa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on aPTT (activated partial thromboplastin time)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of aPTT (activated partial thromboplastin time)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on HepTest (coagulation test)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of HepTest (coagulation test)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on PiCT (prothrombinase-induced clotting time)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of PiCT (prothrombinase-induced clotting time)
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on ETP (endogenous thrombin potential) AUC
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) AUC
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on ETP (endogenous thrombin potential) lag time
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) lag time
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on ETP (endogenous thrombin potential) peak
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) peak
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on ETP (endogenous thrombin potential) peak time
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) peak time
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on Factor VIIa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of Factor VIIa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Emax (maximum effect) on Factor IIa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of Factor IIa activity
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration versus time curve from time 0 to 24 hours [AUC(0-24)] of rivaroxaban after first dose
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
    enhanced_encryption
    Safety Issue:
    No
  • Maximum drug concentration in plasma (Cmax) of rivaroxaban after first dose
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
    enhanced_encryption
    Safety Issue:
    No
  • Half life associated with terminal slope (t1/2) of R-warfarin after the last dose of warfarin
    date_rangeTime Frame:
    Blood samples taken at 24, 30, 48, 54, 72, 96, and 120 h after the last administration of warfarin
    enhanced_encryption
    Safety Issue:
    No
  • Half life associated with terminal slope (t1/2) of S-warfarin after the last dose of warfarin
    date_rangeTime Frame:
    Blood samples taken at 24, 30, 48, 54, 72, 96, and 120 h after the last administration of warfarin
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration versus time curve from time 0 to 24 hours divided by dose per kg body weight [AUC(0-24)norm] of rivaroxaban after first dose
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
    enhanced_encryption
    Safety Issue:
    No
  • Maximum drug concentration in plasma divided by dose per kg body weight (Cmax,norm) of rivaroxaban after first dose
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
    enhanced_encryption
    Safety Issue:
    No
  • Time to reach maximum drug concentration in plasma (tmax) of rivaroxaban after first dose
    date_rangeTime Frame:
    0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
    enhanced_encryption
    Safety Issue:
    No
  • Drug concentration in plasma at expected time of maximum (peak) concentration (Cpeak) of rivaroxaban after second to fourth dose
    date_rangeTime Frame:
    Always 3 h after second, third, and fourth dose
    enhanced_encryption
    Safety Issue:
    No
  • Drug concentration in plasma at expected time of minimum (trough) concentration (Ctrough) of rivaroxaban after second to fourth dose
    date_rangeTime Frame:
    Always 24 h after the second, third, and fourth dose
    enhanced_encryption
    Safety Issue:
    No
  • Half life associated with terminal slope (t1/2) of rivaroxaban after last dose
    date_rangeTime Frame:
    3, 24, 48, and 72 h after the last administration of rivaroxaban
    enhanced_encryption
    Safety Issue:
    No
  • Drug concentration in plasma at steady state at expected time of minimum (trough) concentration (Ctrough,ss) of R-warfarin after the last dose of warfarin
    date_rangeTime Frame:
    0 h (predose) and 24 h after the last administration of warfarin
    enhanced_encryption
    Safety Issue:
    No
  • Drug concentration in plasma at steady state at expected time of minimum (trough) concentration, normalized by dose (Ctrough,ss/D) of R-warfarin after the last dose of warfarin
    date_rangeTime Frame:
    0 h (predose) and 24 h after the last administration of warfarin
    enhanced_encryption
    Safety Issue:
    No
  • Drug concentration in plasma at steady state at expected time of minimum (trough) concentration (Ctrough,ss) of S-warfarin after the last dose of warfarin
    date_rangeTime Frame:
    0 h (predose) and 24 h after the last administration of warfarin
    enhanced_encryption
    Safety Issue:
    No
  • Drug concentration in plasma at steady state at expected time of minimum (trough) concentration, normalized by dose (Ctrough,ss/D) of S-warfarin after the last dose of warfarin
    date_rangeTime Frame:
    0 h (predose) and 24 h after the last administration of warfarin
    enhanced_encryption
    Safety Issue:
    No

Trial design

Randomized, placebo-controlled, parallel-group study in healthy male subjects to investigate the pharmacodynamics during the switching procedure from warfarin to rivaroxaban
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Other
Allocation
Randomized
Blinding
Single Blind
Assignment
Parallel Assignment
Trial Arms
3

Additional Information

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