Thrombosis
Conditions
Keywords
Thromboembolism, Fontan Procedure, Children
Brief summary
The Purpose of this study is to characterize the single and multiple-dose pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/ PD) profiles after oral rivaroxaban therapy administered to pediatric participants 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment (Part A) and to evaluate the safety and efficacy of rivaroxaban, administered twice daily (exposure matched to rivaroxaban 10 milligram \[mg\] once daily in adults) compared to acetylsalicylic acid (ASA), given once daily (approximately 5 milligram per kilogram \[mg/kg\]) for thromboprophylaxis in pediatric participants 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment.
Detailed description
Part A: This part includes a 12-day Initial PK, PD, and Safety Assessment Period. Participants in Part A will not participate in Part B. Randomization in Part B of this study will begin once the cumulative data from the Initial PK, PD, and Safety Assessment Period in Part A are deemed acceptable by the Independent Data Monitoring Committee. Part A of the study will consist of an up to 21-day Screening Period, a 12-day Initial PK, PD, and Safety Assessment Period, a 12-month Open-Label Treatment Period, and a 30-day Follow-Up phone contact. Part B: Participants will be randomly assigned to two treatment groups and randomization ratio will be 2:1 for rivaroxaban and ASA. ASA will be used as control. There will be an up to a 21-day Screening Period, a 12 month Open-Label Treatment Period and a 30-day Follow-Up phone contact.
Interventions
DRUGRivaroxaban
Participants will receive oral suspension containing rivaroxaban 1 milligram per milliliter (mg/ml) twice daily in Part A and Part B. Following total daily doses of Rivaroxaban will be administered based on the weight of the participants: 7 to \<8 kilogram (kg) will receive 2.2 milligram (mg); 8 to \<10 kg will receive 3.2 mg; 10 to\<12 kg will receive 3.4 mg; 12 to \<20 will receive 4.0 mg and 20 to \<30 will receive 5.0 mg.
DRUGAcetylsalicylic Acid
Participants will receive 5 milligram per kilogram (mg/kg) of acetylsalicylic acid once daily up to 12 months in Part B.
Sponsors
Bayer
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 8 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be considered to be clinically stable by the investigator and able to tolerate oral or enteral administration of a suspension formulation and oral/enteral feedings * Satisfactory initial post-Fontan transthoracic echocardiographic Screening as defined in the Post-Fontan Echocardiographic Examination Research Protocol * Parent/legally acceptable representative must sign an informed consent form (ICF) and child assent will also be provided, if applicable, according to local requirements
Exclusion criteria
* Evidence of thrombosis, including those that are asymptomatic confirmed by post-Fontan procedure transthoracic echocardiogram, or other imaging techniques, during the Screening period of the study * History of gastrointestinal disease or surgery associated with clinically relevant impaired absorption * History of or signs/symptoms suggestive of protein-losing enteropathy * Active bleeding or high risk for bleeding contraindicating antiplatelet or anticoagulant therapy, including a history of intracranial bleeding * Platelet count less than (\<)50\*10\^9/Liters (L) at Screening * Estimated glomerular filtration rate (eGFR) \<30 milliliters per minute per 1.73 meter square (mL/min/1.73m\^2) * Known clinically significant liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-FXa at Month 3 (2.5-4 Hours Postdose) | Month 3: 2.5-4 hours postdose | Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Month 3 (Up to 3 Hours Predose) | Month 3: Up to 3 hours predose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Month 3 (0.5-1.5 Hours Postdose) | Month 3: 0.5-1.5 hours postdose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Up to 12 months | Thrombotic event was defined as the appearance of a new thrombotic burden within the cardiovascular system on either routine surveillance or clinically indicated imaging, or the occurrence of a clinical event known to be strongly associated with thrombus (such as cardioembolic stroke, pulmonary embolism). The event included ischemic stroke, pulmonary embolism, venous thrombosis, arterial/intracardiac thrombosis, and other thrombosis. |
| Plasma Concentration of Rivaroxaban at Day 1 (0.5-1.5 Hours Postdose) | Day 1: 0.5-1.5 hours postdose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Day 1 (1.5-4 Hours Postdose) | Day 1: 1.5-4 hours postdose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Day 4 (Up to 3 Hours Predose) | Day 4: Up to 3 hours predose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Day 4 (0.5-1.5 Hours Postdose) | Day 4: 0.5-1.5 hours postdose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Day 4 (1.5-4 Hours Postdose) | Day 4: 1.5-4 hours postdose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Day 4 (6-8 Hours Postdose) | Day 4: 6-8 hours postdose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Plasma Concentration of Rivaroxaban at Month 3 (2.5-4 Hours Postdose) | Month 3: 2.5-4 hours postdose | Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Percentage of Participants With Bleeding Events | Up to 12 months | Bleeding events were categorized into major, clinically relevant non-major bleeding (CRNM), and trivial bleeding events. Major bleeding: overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more; or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults; or occurring in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or contributing to death. CRNM bleeding: overt bleeding not meeting the criteria for major bleeding but associated with: Medical intervention, or Unscheduled contact with a physician, cessation of study treatment, or Discomfort for the subject such as pain, or Impairment of activities of daily life. Trivial bleeding: any other overt bleeding event that does not meet criteria for CRNM bleeding. |
| Absolute Prothrombin Time (PT) at Day 1 (0.5-1.5 Hours Postdose) | Day 1: 0.5-1.5 hours postdose | Absolute prothrombin time was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Absolute PT at Day 1 (1.5-4 Hours Postdose) | Day 1: 1.5-4 hours postdose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Absolute PT at Day 4 (Up to 3 Hours Predose) | Day 4: Up to 3 hours predose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here. |
| Absolute PT at Day 4 (0.5-1.5 Hours Postdose) | Day 4: 0.5-1.5 hours postdose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Absolute PT at Day 4 (1.5-4 Hours Postdose) | Day 4: 1.5-4 hours postdose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Absolute PT at Day 4 (6-8 Hours Postdose) | Day 4: 6-8 hours postdose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Absolute PT at Month 3 (Up to 3 Hours Predose) | Month 3: Up to 3 hours predose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Absolute PT at Month 3 (0.5-1.5 Hours Postdose) | Month 3: 0.5-1.5 hours postdose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Absolute PT at Month 3 (2.5-4 Hours Postdose) | Month 3: 2.5-4 hours postdose | Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Activated Partial Thromboplastin Time (aPTT) at Day 1 (0.5-1.5 Hours Postdose) | Day 1: 0.5-1.5 hours postdose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| aPTT at Day 1 (1.5-4 Hours Postdose) | Day 1: 1.5-4 hours postdose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and average of the participants included in the given time-range is presented here. |
| aPTT at Day 4 (Up to 3 Hours Predose) | Day 4: Up to 3 hours predose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| aPTT at Day 4 (0.5-1.5 Hours Postdose) | Day 4: 0.5-1.5 hours postdose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here. |
| aPTT at Day 4 (1.5-4 Hours Postdose) | Day 4: 1.5-4 hours postdose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average for the participants included in the given time-range is presented here. |
| aPTT at Day 4 (6-8 Hours Postdose) | Day 4: 6-8 hours postdose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| aPTT at Month 3 (Up to 3 Hours Predose) | Month 3: Up to 3 hours predose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| aPTT at Month 3 (0.5-1.5 Hours Postdose) | Month 3: 0.5-1.5 hours postdose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| aPTT at Month 3 (2.5-4 Hours Postdose) | Month 3: 2.5-4 hours postdose | aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Anti-FXa at Day 1 (0.5-1.5 Hours Postdose) | Day 1: 0.5-1.5 hours postdose | Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Anti-FXa at Day 1 (1.5-4 Hours Postdose) | Day 1: 1.5-4 hours postdose | Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Anti-FXa at Day 4 (6-8 Hours Postdose) | Day 4: 6-8 hours postdose | Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Anti-FXa at Month 3 (Up to 3 Hours Predose) | Month 3: Up to 3 hours predose | Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
| Anti-FXa at Month 3 (0.5-1.5 Hours Postdose) | Month 3: 0.5-1.5 hours postdose | Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 12 months | TEAEs were defined as those adverse events (AEs) that occurred from the first day of study drug to the last day of study drug + 2 days inclusive. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
Countries
Argentina, Belgium, Brazil, Canada, Japan, Malaysia, Mexico, Netherlands, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban (Part A) Participants received rivaroxaban as 0.1 percent (%) (1 milligram per milliliter \[mg/ml\]) oral suspension with target exposure matching to that of rivaroxaban 10 mg given once daily in adults as per participant's body weight adjusted total daily dosing administered as two doses 12 hours apart (7 to less than \[\<\] 8 kilograms \[kg\] participant received 2.2 mg; 8 to \<10 kg received 3.2 mg; 10 to \<12 kg received 3.4 mg; 12 to \<20 kg received 4.0 mg; and 20 to \<30 kg received 5.0 mg) (morning and evening dosing), up to 12 months. | 12 |
| Rivaroxaban (Part B) Participants received rivaroxaban as 0.1% (1 mg/ml) oral suspension with target exposure matching to that of rivaroxaban 10 mg given once daily in adults as per participant's body weight adjusted total daily dosing administered as two doses 12 hours apart (7 to \<8 kg participant received 2.2 mg; 8 to \<10 kg received 3.2 mg; 10 to \<12 kg received 3.4 mg; 12 to \<20 kg received 4.0 mg and; 20 to \<30 kg received 5.0 mg) (morning and evening dosing), up to 12 months. | 66 |
| Aspirin (Part B) Participants received aspirin (acetylsalicylic acid) 5 mg/kg once daily up to 12 months. | 34 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Rivaroxaban (Part A) | Rivaroxaban (Part B) | Aspirin (Part B) | Total |
|---|---|---|---|---|
| Age, Continuous | 2.5 years STANDARD_DEVIATION 0.67 | 4.1 years STANDARD_DEVIATION 1.74 | 4.2 years STANDARD_DEVIATION 1.8 | 3.9 years STANDARD_DEVIATION 1.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 22 Participants | 11 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 42 Participants | 19 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 14 Participants | 7 Participants | 21 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 8 Participants | 1 Participants | 12 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 40 Participants | 20 Participants | 68 Participants |
| Region of Enrollment ARGENTINA | 0 Participants | 5 Participants | 1 Participants | 6 Participants |
| Region of Enrollment BELGIUM | 0 Participants | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment BRAZIL | 0 Participants | 7 Participants | 10 Participants | 17 Participants |
| Region of Enrollment CANADA | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment JAPAN | 0 Participants | 8 Participants | 1 Participants | 9 Participants |
| Region of Enrollment MALAYSIA | 0 Participants | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment MEXICO | 0 Participants | 6 Participants | 2 Participants | 8 Participants |
| Region of Enrollment NETHERLANDS | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment SPAIN | 5 Participants | 1 Participants | 0 Participants | 6 Participants |
| Region of Enrollment UNITED STATES | 7 Participants | 25 Participants | 8 Participants | 40 Participants |
| Sex: Female, Male Female | 5 Participants | 30 Participants | 11 Participants | 46 Participants |
| Sex: Female, Male Male | 7 Participants | 36 Participants | 23 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 64 | 0 / 34 |
| other Total, other adverse events | 11 / 12 | 48 / 64 | 26 / 34 |
| serious Total, serious adverse events | 6 / 12 | 19 / 64 | 8 / 34 |
Outcome results
Primary
Absolute Prothrombin Time (PT) at Day 1 (0.5-1.5 Hours Postdose)
Absolute prothrombin time was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 1: 0.5-1.5 hours postdose
Population: Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, activated partial thromboplastin time (aPTT), and/or anti-factor Xa (FXa) activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute Prothrombin Time (PT) at Day 1 (0.5-1.5 Hours Postdose) | 15.46 seconds | Standard Deviation 1.9 |
| Rivaroxaban (Part B) | Absolute Prothrombin Time (PT) at Day 1 (0.5-1.5 Hours Postdose) | 18.02 seconds | Standard Deviation 2.58 |
Primary
Absolute PT at Day 1 (1.5-4 Hours Postdose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 1: 1.5-4 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Day 1 (1.5-4 Hours Postdose) | 16.58 seconds | Standard Deviation 1.84 |
| Rivaroxaban (Part B) | Absolute PT at Day 1 (1.5-4 Hours Postdose) | 18.76 seconds | Standard Deviation 2.25 |
Primary
Absolute PT at Day 4 (0.5-1.5 Hours Postdose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 0.5-1.5 hours postdose
Population: Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Day 4 (0.5-1.5 Hours Postdose) | 17.95 seconds | Standard Deviation 2.1 |
Primary
Absolute PT at Day 4 (1.5-4 Hours Postdose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 1.5-4 hours postdose
Population: Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Day 4 (1.5-4 Hours Postdose) | 18.73 seconds | Standard Deviation 3.3 |
Primary
Absolute PT at Day 4 (6-8 Hours Postdose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 6-8 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Day 4 (6-8 Hours Postdose) | 16.13 seconds | Standard Deviation 2.13 |
Primary
Absolute PT at Day 4 (Up to 3 Hours Predose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here.
Time frame: Day 4: Up to 3 hours predose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Day 4 (Up to 3 Hours Predose) | 15.21 seconds | Standard Deviation 1.54 |
Primary
Absolute PT at Month 3 (0.5-1.5 Hours Postdose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 0.5-1.5 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Month 3 (0.5-1.5 Hours Postdose) | 20.13 seconds | Standard Deviation 3.55 |
| Rivaroxaban (Part B) | Absolute PT at Month 3 (0.5-1.5 Hours Postdose) | 18.89 seconds | Standard Deviation 3.69 |
Primary
Absolute PT at Month 3 (2.5-4 Hours Postdose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 2.5-4 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Month 3 (2.5-4 Hours Postdose) | 19.14 seconds | Standard Deviation 2.61 |
| Rivaroxaban (Part B) | Absolute PT at Month 3 (2.5-4 Hours Postdose) | 19.69 seconds | Standard Deviation 2.81 |
Primary
Absolute PT at Month 3 (Up to 3 Hours Predose)
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: Up to 3 hours predose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Absolute PT at Month 3 (Up to 3 Hours Predose) | 17.59 seconds | Standard Deviation 2.65 |
| Rivaroxaban (Part B) | Absolute PT at Month 3 (Up to 3 Hours Predose) | 16.45 seconds | Standard Deviation 2.27 |
Primary
Activated Partial Thromboplastin Time (aPTT) at Day 1 (0.5-1.5 Hours Postdose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 1: 0.5-1.5 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Activated Partial Thromboplastin Time (aPTT) at Day 1 (0.5-1.5 Hours Postdose) | 31.4 seconds | Standard Deviation 4.68 |
| Rivaroxaban (Part B) | Activated Partial Thromboplastin Time (aPTT) at Day 1 (0.5-1.5 Hours Postdose) | 30.69 seconds | Standard Deviation 8.23 |
Primary
Anti-FXa at Day 1 (0.5-1.5 Hours Postdose)
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 1: 0.5-1.5 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Anti-FXa at Day 1 (0.5-1.5 Hours Postdose) | 66.93 mcg/L | Standard Deviation 23.9 |
| Rivaroxaban (Part B) | Anti-FXa at Day 1 (0.5-1.5 Hours Postdose) | 99.46 mcg/L | Standard Deviation 60.6 |
Primary
Anti-FXa at Day 1 (1.5-4 Hours Postdose)
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 1: 1.5-4 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Anti-FXa at Day 1 (1.5-4 Hours Postdose) | 74.06 mcg/L | Standard Deviation 32.4 |
| Rivaroxaban (Part B) | Anti-FXa at Day 1 (1.5-4 Hours Postdose) | 104.57 mcg/L | Standard Deviation 55.5 |
Primary
Anti-FXa at Day 4 (6-8 Hours Postdose)
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 6-8 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Anti-FXa at Day 4 (6-8 Hours Postdose) | 74.21 mcg/L | Standard Deviation 60.6 |
Primary
Anti-FXa at Month 3 (0.5-1.5 Hours Postdose)
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 0.5-1.5 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part B) | Anti-FXa at Month 3 (0.5-1.5 Hours Postdose) | 110.90 mcg/L | Standard Deviation 75.8 |
Primary
Anti-FXa at Month 3 (2.5-4 Hours Postdose)
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 2.5-4 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part B) | Anti-FXa at Month 3 (2.5-4 Hours Postdose) | 93.48 mcg/L | Standard Deviation 50.3 |
Primary
Anti-FXa at Month 3 (Up to 3 Hours Predose)
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: Up to 3 hours predose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Anti-FXa at Month 3 (Up to 3 Hours Predose) | 60.51 mcg/L | Standard Deviation 29.4 |
| Rivaroxaban (Part B) | Anti-FXa at Month 3 (Up to 3 Hours Predose) | 53.41 mcg/L | Standard Deviation 15 |
Primary
aPTT at Day 1 (1.5-4 Hours Postdose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and average of the participants included in the given time-range is presented here.
Time frame: Day 1: 1.5-4 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Day 1 (1.5-4 Hours Postdose) | 32.83 seconds | Standard Deviation 3.79 |
| Rivaroxaban (Part B) | aPTT at Day 1 (1.5-4 Hours Postdose) | 30.25 seconds | Standard Deviation 3.8 |
Primary
aPTT at Day 4 (0.5-1.5 Hours Postdose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here.
Time frame: Day 4: 0.5-1.5 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Day 4 (0.5-1.5 Hours Postdose) | 36.17 seconds | Standard Deviation 6.99 |
Primary
aPTT at Day 4 (1.5-4 Hours Postdose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average for the participants included in the given time-range is presented here.
Time frame: Day 4: 1.5-4 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Day 4 (1.5-4 Hours Postdose) | 37.58 seconds | Standard Deviation 8.45 |
Primary
aPTT at Day 4 (6-8 Hours Postdose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 6-8 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Day 4 (6-8 Hours Postdose) | 32.83 seconds | Standard Deviation 5.94 |
Primary
aPTT at Day 4 (Up to 3 Hours Predose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: Up to 3 hours predose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Day 4 (Up to 3 Hours Predose) | 33.08 seconds | Standard Deviation 5.68 |
Primary
aPTT at Month 3 (0.5-1.5 Hours Postdose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 0.5-1.5 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Month 3 (0.5-1.5 Hours Postdose) | 26.60 seconds | Standard Deviation 2.55 |
| Rivaroxaban (Part B) | aPTT at Month 3 (0.5-1.5 Hours Postdose) | 31.15 seconds | Standard Deviation 4.17 |
Primary
aPTT at Month 3 (2.5-4 Hours Postdose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 2.5-4 hours postdose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Month 3 (2.5-4 Hours Postdose) | 26.74 seconds | Standard Deviation 1.79 |
| Rivaroxaban (Part B) | aPTT at Month 3 (2.5-4 Hours Postdose) | 31.67 seconds | Standard Deviation 3.58 |
Primary
aPTT at Month 3 (Up to 3 Hours Predose)
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: Up to 3 hours predose
Population: PD analysis set included all participants who received at least 1 dose of study drug and had quantifiable and time-matched PT, aPTT, and/or anti-FXa activity values were included in the descriptive PD analysis. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | aPTT at Month 3 (Up to 3 Hours Predose) | 25.36 seconds | Standard Deviation 3.76 |
| Rivaroxaban (Part B) | aPTT at Month 3 (Up to 3 Hours Predose) | 28.70 seconds | Standard Deviation 3.76 |
Primary
Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic)
Thrombotic event was defined as the appearance of a new thrombotic burden within the cardiovascular system on either routine surveillance or clinically indicated imaging, or the occurrence of a clinical event known to be strongly associated with thrombus (such as cardioembolic stroke, pulmonary embolism). The event included ischemic stroke, pulmonary embolism, venous thrombosis, arterial/intracardiac thrombosis, and other thrombosis.
Time frame: Up to 12 months
Population: Full analysis set included all participants in Part A who received at least 1 dose of study drug and all participants in Part B who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban (Part A) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Any thrombotic event | 8.3 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Ischemic stroke | 0 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Pulmonary embolism | 0 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Venous thrombosis | 8.3 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Arterial/intracardiac thrombosis | 0 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Other thrombosis | 0 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Other thrombosis | 0 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Any thrombotic event | 1.6 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Venous thrombosis | 0 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Arterial/intracardiac thrombosis | 0 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Ischemic stroke | 0 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Pulmonary embolism | 1.6 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Ischemic stroke | 2.9 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Pulmonary embolism | 0 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Other thrombosis | 0 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Venous thrombosis | 5.9 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Any thrombotic event | 8.8 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) | Arterial/intracardiac thrombosis | 0 percentage of participants |
Primary
Percentage of Participants With Bleeding Events
Bleeding events were categorized into major, clinically relevant non-major bleeding (CRNM), and trivial bleeding events. Major bleeding: overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more; or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults; or occurring in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or contributing to death. CRNM bleeding: overt bleeding not meeting the criteria for major bleeding but associated with: Medical intervention, or Unscheduled contact with a physician, cessation of study treatment, or Discomfort for the subject such as pain, or Impairment of activities of daily life. Trivial bleeding: any other overt bleeding event that does not meet criteria for CRNM bleeding.
Time frame: Up to 12 months
Population: Safety analysis set included all participants in Part A who received at least 1 dose of study drug and all participants in Part B who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban (Part A) | Percentage of Participants With Bleeding Events | Clinically relevant non-major bleeding | 8.3 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Bleeding Events | Any bleeding event | 33.3 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Bleeding Events | Trivial bleeding | 25.0 percentage of participants |
| Rivaroxaban (Part A) | Percentage of Participants With Bleeding Events | Major Bleeding | 0 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Bleeding Events | Clinically relevant non-major bleeding | 6.3 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Bleeding Events | Major Bleeding | 1.6 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Bleeding Events | Any bleeding event | 35.9 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Bleeding Events | Trivial bleeding | 32.8 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Bleeding Events | Major Bleeding | 0 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Bleeding Events | Any bleeding event | 41.2 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Bleeding Events | Trivial bleeding | 35.3 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Bleeding Events | Clinically relevant non-major bleeding | 8.8 percentage of participants |
Primary
Plasma Concentration of Rivaroxaban at Day 1 (0.5-1.5 Hours Postdose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 1: 0.5-1.5 hours postdose
Population: Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Day 1 (0.5-1.5 Hours Postdose) | 46.69 micrograms per liter (mcg/L) | Standard Deviation 39.4 |
| Rivaroxaban (Part B) | Plasma Concentration of Rivaroxaban at Day 1 (0.5-1.5 Hours Postdose) | 92.86 micrograms per liter (mcg/L) | Standard Deviation 72.6 |
Primary
Plasma Concentration of Rivaroxaban at Day 1 (1.5-4 Hours Postdose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 1: 1.5-4 hours postdose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Day 1 (1.5-4 Hours Postdose) | 86.62 mcg/L | Standard Deviation 43.1 |
| Rivaroxaban (Part B) | Plasma Concentration of Rivaroxaban at Day 1 (1.5-4 Hours Postdose) | 103.61 mcg/L | Standard Deviation 62.6 |
Primary
Plasma Concentration of Rivaroxaban at Day 4 (0.5-1.5 Hours Postdose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 0.5-1.5 hours postdose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Day 4 (0.5-1.5 Hours Postdose) | 107.58 mcg/L | Standard Deviation 54.2 |
Primary
Plasma Concentration of Rivaroxaban at Day 4 (1.5-4 Hours Postdose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 1.5-4 hours postdose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Day 4 (1.5-4 Hours Postdose) | 147.18 mcg/L | Standard Deviation 116 |
Primary
Plasma Concentration of Rivaroxaban at Day 4 (6-8 Hours Postdose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: 6-8 hours postdose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Day 4 (6-8 Hours Postdose) | 66.81 mcg/L | Standard Deviation 64.6 |
Primary
Plasma Concentration of Rivaroxaban at Day 4 (Up to 3 Hours Predose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Day 4: Up to 3 hours predose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Day 4 (Up to 3 Hours Predose) | 36.58 mcg/L | Standard Deviation 37.4 |
Primary
Plasma Concentration of Rivaroxaban at Month 3 (0.5-1.5 Hours Postdose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 0.5-1.5 hours postdose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Month 3 (0.5-1.5 Hours Postdose) | 86.25 mcg/L | Standard Deviation 32 |
| Rivaroxaban (Part B) | Plasma Concentration of Rivaroxaban at Month 3 (0.5-1.5 Hours Postdose) | 94.12 mcg/L | Standard Deviation 82.2 |
Primary
Plasma Concentration of Rivaroxaban at Month 3 (2.5-4 Hours Postdose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: 2.5-4 hours postdose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Month 3 (2.5-4 Hours Postdose) | 96.67 mcg/L | Standard Deviation 58.4 |
| Rivaroxaban (Part B) | Plasma Concentration of Rivaroxaban at Month 3 (2.5-4 Hours Postdose) | 102.99 mcg/L | Standard Deviation 56 |
Primary
Plasma Concentration of Rivaroxaban at Month 3 (Up to 3 Hours Predose)
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Time frame: Month 3: Up to 3 hours predose
Population: PK analysis set included all participants who received at least 1 dose of study drug and had quantifiable rivaroxaban plasma concentrations. Here, 'N' (number of participants analyzed) signifies number of participants that were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban (Part A) | Plasma Concentration of Rivaroxaban at Month 3 (Up to 3 Hours Predose) | 38.23 mcg/L | Standard Deviation 25.7 |
| Rivaroxaban (Part B) | Plasma Concentration of Rivaroxaban at Month 3 (Up to 3 Hours Predose) | 29.41 mcg/L | Standard Deviation 25.5 |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as those adverse events (AEs) that occurred from the first day of study drug to the last day of study drug + 2 days inclusive. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time frame: Up to 12 months
Population: Safety analysis set included all participants in Part A who received at least 1 dose of study drug and all participants in Part B who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban (Part A) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 91.7 percentage of participants |
| Rivaroxaban (Part B) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 85.9 percentage of participants |
| Aspirin (Part B) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 85.3 percentage of participants |