Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 15 of 164 for:    warfarin AND Vitamin K

Switching Study From Warfarin to Rivaroxaban

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01507051
Recruitment Status : Completed
First Posted : January 10, 2012
Results First Posted : April 26, 2012
Last Update Posted : February 9, 2015
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE December 5, 2011
First Posted Date  ICMJE January 10, 2012
Results First Submitted Date  ICMJE January 30, 2012
Results First Posted Date  ICMJE April 26, 2012
Last Update Posted Date February 9, 2015
Study Start Date  ICMJE November 2008
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2012)
  • Emax (Maximum Effect) on Prothrombin Time (PT) (Coagulation Test) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Higher values than the baseline indicate anticoagulant effects. Emax on PT was measured as the ratio of maximum PT (measured in seconds) divided by PT (measured in seconds) at baseline.
  • Emax,BA (Baseline Adjusted Maximum Effect) on Prothrombin Time (Coagulation Test) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Higher values than the baseline indicate anticoagulant effects. Emax,BA on PT was measured as maximum PT (measured in seconds) minus PT (measured in seconds) at baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2012)
  • Emax (maximum effect) of Prothrombin time (PT) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax,BA (baseline adjusted maximum effect) of Prothrombin time (PT) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2012)
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of Prothrombin Time (Coagulation Test) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Higher values than the baseline indicate anticoagulant effects. AUC(0-tn) of PT was the area under the measurement (PT [measured in seconds] at different time-points divided by PT [measured in seconds] at baseline) versus time curve from time 0 to the last data point.
  • 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) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Higher values than the baseline indicate anticoagulant effects. AUCBA(0-tn) of PT was the area under the measurement (PT [measured in seconds] at different time-points minus PT [measured in seconds] at baseline) versus time curve from time 0 to the last data point.
  • Emax on PT (Measured as INR=International Normalized Ratio) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Prothrombin time - INR measured in seconds that is calculated as INR which is a correction for PT assay differences and an optimization to measure vitamin K antagonists. Higher values than the baseline indicate anticoagulant effects. Emax on PT (INR) was measured as the ratio of maximum INR divided by baseline INR.
  • 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) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Prothrombin time - INR measured in seconds that is calculated as INR which is a correction for PT assay differences and an optimization to measure vitamin K antagonists. Higher values than the baseline indicate anticoagulant effects. AUC(0-tn) of PT (INR) was the area under the measurement (PT measured as INR at different time-points divided by PT measured as INR at baseline) versus time curve from time 0 to the last data point.
  • Emax on Factor Xa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Test to measure the activity of endogenous Factor Xa. Emax on Factor Xa activity was calculated as 100*(Factor Xa activity at baseline [measured as activity per mL] - minimum of Factor Xa activity [measured as activity per mL]) / Factor Xa activity at baseline [measured as activity per mL].
  • AUC(0-tn) (Area Under the Inverse Measurement Versus Time Curve From Time 0 to the Last Data Point) of Factor Xa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Test to measure the activity of endogenous Factor Xa. AUC(0-tn) of Factor Xa activity was the area under the inverse measurement [100*(Factor Xa activity at baseline (measured as activity per mL) - Factor Xa activity (measured as activity per mL) at different time-points) / Factor Xa activity at baseline (measured as activity per mL)] versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on Anti-Factor Xa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. Higher Values than the baseline indicate a more pronounced inhibition. Emax on anti-Factor Xa activity was measured as the ratio of maximum anti-Factor Xa activity (measured in U/L) divided by anti-Factor Xa activity (measured in U/L) at baseline.
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of Anti-Factor Xa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. Higher Values than the baseline indicate a more pronounced inhibition. AUC(0-tn) of anti-Factor Xa activity was the area under the measurement (anti-Factor Xa activity [measured in U/L] at different time-points divided by anti-Factor Xa activity [measured in U/L] at baseline) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on aPTT (Activated Partial Thromboplastin Time) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V, VIII, IX, X, XI and XII. Higher values than the baseline indicate anticoagulant effects. Emax on aPTT was measured as the ratio of maximum aPTT (measured in seconds) divided by aPTT (measured in seconds) at baseline.
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of aPTT (Activated Partial Thromboplastin Time) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V, VIII, IX, X, XI and XII. Higher values than the baseline indicate anticoagulant effects. AUC(0-tn) of aPTT was the area under the measurement (aPTT [measured in seconds] at different time-points divided by aPTT [measured in seconds] at baseline) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on HepTest (Coagulation Test) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    This coagulation test was developed to monitor heparin and especially low-molecular weight heparins (LMWH). It is sensitive to measure Factor X. Higher values than the baseline indicate anticoagulant effects. Emax on HepTest was measured as the ratio of maximum HepTest (measured in seconds) divided by HepTest (measured in seconds) at baseline.
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of HepTest (Coagulation Test) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    This coagulation test was developed to monitor heparin and especially low-molecular weight heparins (LMWH). It is sensitive to measure Factor X. Higher values than the baseline indicate anticoagulant effects. AUC(0-tn) of HepTest was the area under the measurement (HepTest [measured in seconds] at different time-points divided by HepTest [measured in seconds] at baseline) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on PiCT (Prothrombinase-induced Clotting Time) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    This coagulation test can be adapted to measure different anticoagulants, including inhibitors of Factor X. Higher values than the baseline indicate anticoagulant effects. Emax on PiCT was measured as the ratio of maximum PiCT (measured in seconds) divided by PiCT (measured in seconds) at baseline.
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of PiCT (Prothrombinase-induced Clotting Time) [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    This coagulation test can be adapted to measure different anticoagulants, including inhibitors of Factor X. Higher values than the baseline indicate anticoagulant effects. AUC(0-tn) of PiCT was the area under the measurement (PiCT [measured in seconds] at different time-points divided by PiCT [measured in seconds] at baseline) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on ETP (Endogenous Thrombin Potential) AUC [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP AUC assesses the overall function of the clotting cascade. The AUC assesses the overall ability to generate thrombin. Decreasing values compared to baseline indicate an anticoagulant effect. Emax on ETP AUC was measured as the ratio of ETP AUC (measured in nm*min as integral of fluorescence measurements) at baseline divided by minimum ETP AUC (measured in nm*min as integral of fluorescence measurements).
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of ETP (Endogenous Thrombin Potential) AUC [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP AUC assesses the overall function of the clotting cascade. The AUC assesses the overall ability to generate thrombin. Decreasing values compared to baseline indicate an anticoagulant effect. AUC(0-tn) of ETP AUC was the area under the measurement (ETP AUC [measured in nm*min as integral of fluorescence measurements] at baseline divided by ETP AUC [measured in nm*min as integral of fluorescence measurements] at different time-points) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on ETP (Endogenous Thrombin Potential) Lag Time [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP lag time assesses the overall function of the clotting cascade. The lag time assesses the time required until thrombin is generated. Increasing values compared to baseline indicate an anticoagulant effect. Emax on ETP lag time was measured as the ratio of maximum ETP lag time (in minutes as measure for the start of coagulation) divided by ETP lag time (in minutes as measure for the start of coagulation) at baseline.
  • 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 [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP lag time assesses the overall function of the clotting cascade. The lag time assesses the time required until thrombin is generated. Increasing values compared to baseline indicate an anticoagulant effect. AUC(0-tn) of ETP lag time was the area under the measurement (ETP lag time [in minutes as measure for the start of coagulation] at different time-points divided by ETP lag time [in minutes as measure for the start of coagulation] at baseline) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on ETP (Endogenous Thrombin Potential) Peak [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP peak assesses the overall function of the clotting cascade. The peak assesses the overall maximal ability to generate thrombin. Decreasing values compared to baseline indicate an anticoagulant effect. Emax on ETP peak was measured as the ratio of ETP peak (measured in nm as maximum coagulation activity) at baseline divided by minimum ETP peak (measured in nm as maximum coagulation activity).
  • 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 Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP peak assesses the overall function of the clotting cascade. The peak assesses the overall maximal ability to generate thrombin. Decreasing values compared to baseline indicate an anticoagulant effect. AUC(0-tn) of ETP peak was the area under the measurement (ETP peak [measured in nm as maximum coagulation activity] at baseline divided by ETP peak measured [in nm as maximum coagulation activity] at different time-points) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on ETP (Endogenous Thrombin Potential) Peak Time [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP peak time assesses the overall function of the clotting cascade. The peak time assesses the time required to reach the maximal thrombin generation. Increasing values compared to baseline indicate an anticoagulant effect. Emax on ETP peak time was measured as the ratio of maximum ETP peak time (measured in minutes as time to reach the maximum coagulation activity) divided by ETP peak time (measured in minutes as time to reach the maximum coagulation activity) at baseline.
  • 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 [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    ETP peak time assesses the overall function of the clotting cascade. The peak time assesses the time required to reach the maximal thrombin generation. Increasing values compared to baseline indicate an anticoagulant effect. AUC(0-tn) of ETP peak time was the area under the measurement (ETP peak time [measured in minutes as time to reach the maximum coagulation activity] at different time-points divided by ETP peak time [measured in minutes as time to reach the maximum coagulation activity] at baseline) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on Factor VIIa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Factor VII is a coagulation factor that is required for the coagulation process. Emax on Factor VIIa activity was measured as the ratio of Factor VIIa activity (measured as percent of actual Factor VIIa activity compared to Factor VIIa activity in reference plasma) at baseline divided by minimum Factor VIIa activity (measured as percent of actual Factor VIIa activity compared to Factor VIIa activity in reference plasma).
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of Factor VIIa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Factor VII is a coagulation factor that is required for the coagulation process. AUC(0-tn) of Factor VIIa activity was the area under the measurement (Factor VIIa activity [measured as percent of actual Factor VIIa activity compared to Factor VIIa activity in reference plasma] at baseline divided by Factor VIIa activity [measured as percent of actual Factor VIIa activity compared to Factor VIIa activity in reference plasma] at different time-points) versus time curve from time 0 to the last data point.
  • Emax (Maximum Effect) on Factor IIa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Factor II (Thrombin) is a coagulation factor that is required for the coagulation process. Emax on Factor IIa activity was measured as the ratio of Factor IIa activity (measured as percent of actual Factor IIa activity compared to Factor IIa activity in reference plasma) at baseline divided by minimum Factor IIa activity (measured as percent of actual Factor IIa activity compared to Factor IIa activity in reference plasma).
  • AUC(0-tn) (Area Under the Measurement Versus Time Curve From Time 0 to the Last Data Point) of Factor IIa Activity [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
    Factor II (Thrombin) is a coagulation factor that is required for the coagulation process. AUC(0-tn) of Factor IIa activity was the area under the measurement (Factor IIa activity [measured as percent of actual Factor IIa activity compared to Factor IIa activity in reference plasma] at baseline divided by Factor IIa activity [measured as percent of actual Factor IIa activity compared to Factor IIa activity in reference plasma] at different time-points) versus time curve from time 0 to the last data point.
  • Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours [AUC(0-24)] of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
    The AUC is a measure of systemic drug exposure which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample ([AUC(0-24)] is defined as area under the concentration vs. time curve from zero to 24 hours after first (single) dose).
  • Maximum Drug Concentration in Plasma (Cmax) of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
    Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
  • Half Life Associated With Terminal Slope (t1/2) of R-warfarin After the Last Dose of Warfarin [ Time Frame: Blood samples taken at 24, 30, 48, 54, 72, 96, and 120 h after the last administration of warfarin ]
    Half-life refers to the elimination of the drug, i.e. the time it takes for the blood plasma concentration to reach half the concentration in the terminal phase of elimination.
  • Half Life Associated With Terminal Slope (t1/2) of S-warfarin After the Last Dose of Warfarin [ Time Frame: Blood samples taken at 24, 30, 48, 54, 72, 96, and 120 h after the last administration of warfarin ]
    Half-life refers to the elimination of the drug, i.e. the time it takes for the blood plasma concentration to reach half the concentration in the terminal phase of elimination.
  • 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 [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
    The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; [AUC(0-24)norm] is defined as AUC divided by dose per kg body weight from zero to 24 hours after first (single) dose.
  • Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
    Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; Cmax,norm is defined as Cmax divided by dose (mg) per kg body weight.
  • Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
  • Drug Concentration in Plasma at Expected Time of Maximum (Peak) Concentration (Cpeak) of Rivaroxaban After Second to Fourth Dose [ Time Frame: Always 3 h after second, third, and fourth dose ]
    Cpeak refers to the time after dosing when the drug concentration is expected to reach its maximum (peak) concentration.
  • Drug Concentration in Plasma at Expected Time of Minimum (Trough) Concentration (Ctrough) of Rivaroxaban After Second to Fourth Dose [ Time Frame: Always 24 h after the second, third, and fourth dose ]
    Ctrough refers to the time after dosing when the drug concentration is expected to reach its minimum (trough) concentration.
  • Half Life Associated With Terminal Slope (t1/2) of Rivaroxaban After Last Dose [ Time Frame: 3, 24, 48, and 72 h after the last administration of rivaroxaban ]
    Half-life refers to the elimination of the drug, i.e. the time it takes for the blood plasma concentration to reach half the concentration in the terminal phase of elimination.
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
    Ctrough,ss refers to the drug concentration at steady state at the time when it is expected to reach its minimum (trough) concentration.
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
    Ctrough,ss/D refers to the drug concentration at steady state at the time when it is expected to reach its minimum (trough) concentration, normalized by dose.
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
    Ctrough,ss refers to the drug concentration at steady state at the time when it is expected to reach its minimum (trough) concentration.
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
    Ctrough,ss/D refers to the drug concentration at steady state at the time when it is expected to reach its minimum (trough) concentration, normalized by dose.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2012)
  • AUC(0-tn) (area under the plasma concentration versus time curve from time 0 to the last data point) of Prothrombin time (PT) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUCBA(0-tn) (baseline adjusted area under the plasma concentration versus time curve from time 0 to the last data point) of Prothrombin time (PT) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax for PT (INR [international normalized ratio]) increase [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) for PT (INR [international normalized ratio]) increase [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of Factor Xa activity inhibition [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of Factor Xa activity inhibition [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of anti-Factor Xa activity increase [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of anti-Factor Xa activity increase [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of aPTT (activated partial thromboplastin time) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of aPTT (activated partial thromboplastin time) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of HepTest prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of HepTest prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of PiCT (prothrombinase-induced clotting time) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of PiCT (prothrombinase-induced clotting time) prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of ETP (endogenous thrombin potential) AUC reduction [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of ETP (endogenous thrombin potential) AUC reduction [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of ETP (endogenous thrombin potential) lag time prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of ETP (endogenous thrombin potential) lag time prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of ETP (endogenous thrombin potential) peak reduction [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of ETP (endogenous thrombin potential) peak reduction [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of ETP (endogenous thrombin potential) peak time prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of ETP (endogenous thrombin potential) peak time prolongation [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of Factor VIIa activity inhibition [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of Factor VIIa activity inhibition [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Emax of Factor IIa activity inhibition [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • AUC(0-tn) of Factor IIa activity inhibition [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo ]
  • Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours [AUC(0-24)] of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
  • Maximum Drug Concentration in Plasma (Cmax) of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
  • Half Life Associated With Terminal Slope (t1/2) of R-warfarin After the Last Dose of Warfarin [ Time Frame: Blood samples taken at 24, 30, 48, 54, 72, 96, and 120 h after the last administration of warfarin ]
  • Half Life Associated With Terminal Slope (t1/2) of S-warfarin After the Last Dose of Warfarin [ Time Frame: Blood samples taken at 24, 30, 48, 54, 72, 96, and 120 h after the last administration of warfarin ]
  • 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 [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
  • Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
  • Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Rivaroxaban After First Dose [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban ]
  • Drug Concentration in Plasma at Expected Time of Maximum (Peak) Concentration (Cpeak) of Rivaroxaban After Second to Fourth Dose [ Time Frame: Always 3 h after second, third, and fourth dose ]
  • Drug Concentration in Plasma at Expected Time of Minimum (Trough) Concentration (Ctrough) of Rivaroxaban After Second to Fourth Dose [ Time Frame: Always 24 h after the second, third, and fourth dose ]
  • Half Life Associated With Terminal Slope (t1/2) of Rivaroxaban After Last Dose [ Time Frame: 3, 24, 48, and 72 h after the last administration of rivaroxaban ]
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
  • 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 [ Time Frame: 0 h (predose) and 24 h after the last administration of warfarin ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Switching Study From Warfarin to Rivaroxaban
Official Title  ICMJE Randomized, Placebo-controlled, Parallel-group Study in Healthy Male Subjects to Investigate the Pharmacodynamics During the Switching Procedure From Warfarin to Rivaroxaban
Brief Summary

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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Condition  ICMJE Venous Thrombosis
Intervention  ICMJE
  • Drug: 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
  • Drug: Rivaroxaban (Xarelto, BAY59-7939)
    Days 0 to 3: 20 mg rivaroxaban once daily
  • Drug: Placebo
    Days 0 to 3: 1 tablet placebo, identical to active tablet
  • Drug: Vitamin K (Konakion)
    Day 5: 10 mg vitamin K (Konakion) once daily
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • Drug: Warfarin (Coumadin)
    • Drug: Rivaroxaban (Xarelto, BAY59-7939)
    • Drug: Vitamin K (Konakion)
  • Placebo Comparator: 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
    Interventions:
    • Drug: Warfarin (Coumadin)
    • Drug: Placebo
    • Drug: Vitamin K (Konakion)
  • Active Comparator: Rivaroxaban (Xarelto, BAY59-7939)
    Days 0 to 3: 20 mg rivaroxaban once daily
    Intervention: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Publications * Kubitza D, Becka M, Mück W, Krätzschmar 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 6, 2012)
96
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2009
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01507051
Other Study ID Numbers  ICMJE 10849
2008-005540-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP