Trial Condition(s):
Venous thrombosis
Switching study from warfarin to rivaroxaban
Bayer Identifier:
10849
ClinicalTrials.gov Identifier:
EudraCT Number:
EU CT Number:
Not Available
Study Completed
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.
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 Summary
Enrollment Goal
96
Trial Dates
Phase
1
Could I receive a placebo?
Yes
Products
Xarelto (Rivaroxaban, BAY59-7939)
Accepts Healthy Volunteers
Yes
Where to Participate
Loading...
Locations
| Locations | |
|---|---|
Locations MEDA Manufacturing GmbH, ClinPharmCologne Köln, Germany, 51063 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations CRS Clinical-Research-Services Mönchengladbach GmbH Mönchengladbach, Germany, 41061 | Contact Us: E-mail: [email protected] Phone: Not Available |
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
Primary Outcome
- Emax (maximum effect) on Prothrombin Time (PT) (coagulation test)Timeframe: 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) on Prothrombin time (coagulation test)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
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)Timeframe: 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 measurement versus time curve from time 0 to the last data point) of Prothrombin time (coagulation test)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax on PT (measured as INR=International Normalized Ratio)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- 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)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax on Factor Xa activityTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the inverse measurement versus time curve from time 0 to the last data point) of Factor Xa activityTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on anti-Factor Xa activityTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of anti-Factor Xa activityTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on aPTT (activated partial thromboplastin time)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of aPTT (activated partial thromboplastin time)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on HepTest (coagulation test)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of HepTest (coagulation test)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on PiCT (prothrombinase-induced clotting time)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of PiCT (prothrombinase-induced clotting time)Timeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on ETP (endogenous thrombin potential) AUCTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) AUCTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on ETP (endogenous thrombin potential) lag timeTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) lag timeTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on ETP (endogenous thrombin potential) peakTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) peakTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on ETP (endogenous thrombin potential) peak timeTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of ETP (endogenous thrombin potential) peak timeTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on Factor VIIa activityTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of Factor VIIa activityTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- Emax (maximum effect) on Factor IIa activityTimeframe: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban or placebo
- AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of Factor IIa activityTimeframe: 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 doseTimeframe: 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 doseTimeframe: 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 warfarinTimeframe: 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 warfarinTimeframe: 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 doseTimeframe: 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 doseTimeframe: 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 doseTimeframe: 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 doseTimeframe: 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 doseTimeframe: Always 24 h after the second, third, and fourth dose
- Half life associated with terminal slope (t1/2) of rivaroxaban after last doseTimeframe: 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 warfarinTimeframe: 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 warfarinTimeframe: 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 warfarinTimeframe: 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 warfarinTimeframe: 0 h (predose) and 24 h after the last administration of warfarin
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