Venous Thrombosis
Conditions
Brief summary
The purpose of this study is to find out whether rivaroxaban is safe to use in children and how long it stays in the body. There will also be a check for bleeding and worsening of blood clots.
Interventions
DRUGRivaroxaban (Xarelto, BAY59-7939)
Subjects were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days.
DRUGActive comparator
Subjects received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or international normalized ratio (INR) adjusted (vitamin K antagonist).
DRUGRivaroxaban (BAY59-7939) suspension
Subjects aged were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily.
Sponsors
Janssen Research & Development, LLC
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Children aged 6 to \< 18 years with documented symptomatic or asymptomatic venous thrombosis treated for at least 2 months or, in case of catheter related thrombosis, treated for at least 6 weeks with LMWH (low molecular weight heparin), , fondaparinux and/or VKA (vitamin K antagonist). * Informed consent provided and, if applicable, child assent provided
Exclusion criteria
* Active bleeding or high risk for bleeding contraindicating anticoagulant therapy * Symptomatic progression of venous thrombosis during preceding anticoagulant treatment * Planned invasive procedures, including lumbar puncture and removal of non peripherally placed central lines during study treatment * An estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 * Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk or ALT \> 5x upper level of normal (ULN) or total bilirubin \> 2x ULN with direct bilirubin \> 20% of the total * Platelet count \< 50 x 10\^9/L * Hypertension defined as \> 95th age percentile * Life expectancy \< 3 months * Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e. all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically * Concomitant use of strong inducers of CYP3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | From start of study drug administration until end of the 30-day treatment period | Central independent adjudication committee (CIAC) classified bleeding as follows: Major bleeding is defined as overt bleeding and: * associated with a fall in hemoglobin of 2 gram/decilitre (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, e.g. intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or * contributing to death. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding, but associated with: * medical intervention, or * unscheduled contact (visit or telephone call) with a physician, or * cessation (temporary) of study treatment, or * discomfort for the child such as pain or * impairment of activities of daily life (such as loss of school days or hospitalization). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Repeat imaging at the end of the 30 day treatment period | The occurrence of asymptomatic deterioration in thrombotic burden was summarized by age group. Asymptomatic deterioration in thrombotic burden was documented by the appropriate imaging test and the results were classified as normalized, improved, no relevant change, deteriorated, not evaluable or not available. |
| Change From Baseline in Prothrombin Time at Specified Time Points | 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 | Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade. |
| Number of Subjects With Symptomatic Recurrent Venous Thromboembolism | From start of study drug administration until end of the 30-day treatment period | The occurrence of recurrent venous thromboembolism was summarized by age group. Symptomatic recurrence of venous thrombosis was documented by the appropriate imaging test. |
| Anti-factor Xa Values at Specified Time Points | 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 | The individual anti-Factor Xa activity was determined ex-vivo using a photometric method. |
| Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 | Geometric and percentage geometric coefficient of variation (%CV) were reported. |
| Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 | The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway. |
Countries
Australia, Austria, Canada, France, Germany, Israel, Italy, Netherlands, Switzerland, United States
Participant flow
Recruitment details
The study was conducted at multiple centers in 10 countries worldwide between 19 February 2013 (first subject first visit) and 01 September 2016 (last subject last visit).
Pre-assignment details
A total of 68 subjects were screened, of these 4 subjects failed screening. The remaining 64 subjects were randomized, of whom 63 subjects were treated.
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years Subjects aged from 12 - \<18 years were administered with age and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days. Subjects with a body weight of 14 to less than 50 kilogram (kg) received a dose (equivalent to 20 milligram \[mg\] in adults) ranging from 5 to 15 mg, and subjects with a body weight (comparable to adults) of greater than or equal to 50 kg received a dose of 20 mg. | 11 |
| Comparator, Age: 12 - <18 Years Subjects aged from 12 - \<18 years received comparator as per standard of care. | 13 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years Subjects aged from 6 - \<12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days. | 13 |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years Subjects aged from 6 - \<12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily. Subjects with a body weight of 9 to less than 50 kg received a total daily dose (equivalent to 20 mg in adults) ranging from 6.4 to 15 mg and subjects with a body weight of greater than or equal to 50 kg received a total daily dose of 20 mg. | 19 |
| Comparator, Age: 6 - < 12 Years Subjects aged from 6 - \< 12 years received comparator as per standard of care. | 7 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Comparator, Age: 12 - <18 Years | Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Comparator, Age: 6 - < 12 Years | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 15.5 Years STANDARD_DEVIATION 1.2 | 14.8 Years STANDARD_DEVIATION 1 | 8.5 Years STANDARD_DEVIATION 2.1 | 8.3 Years STANDARD_DEVIATION 1.9 | 9.0 Years STANDARD_DEVIATION 2 | 11.0 Years STANDARD_DEVIATION 3.7 |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 5 Participants | 6 Participants | 3 Participants | 29 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 8 Participants | 13 Participants | 4 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 11 | 8 / 13 | 6 / 13 | 12 / 19 | 2 / 7 |
| serious Total, serious adverse events | 0 / 11 | 1 / 13 | 0 / 13 | 2 / 19 | 0 / 7 |
Outcome results
Primary
Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events
Central independent adjudication committee (CIAC) classified bleeding as follows: Major bleeding is defined as overt bleeding and: * associated with a fall in hemoglobin of 2 gram/decilitre (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, e.g. intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or * contributing to death. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding, but associated with: * medical intervention, or * unscheduled contact (visit or telephone call) with a physician, or * cessation (temporary) of study treatment, or * discomfort for the child such as pain or * impairment of activities of daily life (such as loss of school days or hospitalization).
Time frame: From start of study drug administration until end of the 30-day treatment period
Population: Full analysis set. Data was evaluated only for subjects who received active study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Major bleeding events | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Clinically relevant non-major bleeding events | 3 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Major bleeding events | 0 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Clinically relevant non-major bleeding events | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Major bleeding events | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Clinically relevant non-major bleeding events | 0 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Clinically relevant non-major bleeding events | 1 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Major bleeding events | 0 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Major bleeding events | 0 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events | Clinically relevant non-major bleeding events | 0 Participants |
Secondary
Anti-factor Xa Values at Specified Time Points
The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.
Time frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Population: Pharmacodynamic analysis set (N=42) included all subjects with at least one blood sample for clotting parameters in accordance with the pharmacodynamic sampling strategy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA microgram per liter (mcg/L) | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 15: 6 to 8 hours post-dose | 105.223 microgram per liter (mcg/L) | Standard Deviation 54.339 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 15: pre-dose | 16.081 microgram per liter (mcg/L) | Standard Deviation 6.136 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 15: 2 to 4 hours post-dose | 185.481 microgram per liter (mcg/L) | Standard Deviation 53.326 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 31: 20 to 24 hours post-dose | 16.038 microgram per liter (mcg/L) | Standard Deviation 7.653 |
| Comparator, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 15: 6 to 8 hours post-dose | 68.670 microgram per liter (mcg/L) | Standard Deviation 32.845 |
| Comparator, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 15: pre-dose | 8.136 microgram per liter (mcg/L) | Standard Deviation 3.069 |
| Comparator, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 15: 2 to 4 hours post-dose | 252.853 microgram per liter (mcg/L) | Standard Deviation 71.072 |
| Comparator, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA microgram per liter (mcg/L) | — |
| Comparator, Age: 12 - <18 Years | Anti-factor Xa Values at Specified Time Points | Day 31: 20 to 24 hours post-dose | 8.409 microgram per liter (mcg/L) | Standard Deviation 3.664 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Anti-factor Xa Values at Specified Time Points | Day 31: 20 to 24 hours post-dose | NA microgram per liter (mcg/L) | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Anti-factor Xa Values at Specified Time Points | Day 31: 10 to 16 hours post-dose | 30.927 microgram per liter (mcg/L) | Standard Deviation 18.037 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Anti-factor Xa Values at Specified Time Points | Day 15: pre-dose | 31.553 microgram per liter (mcg/L) | Standard Deviation 25.416 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Anti-factor Xa Values at Specified Time Points | Day 15: 6 to 8 hours post-dose | 77.929 microgram per liter (mcg/L) | Standard Deviation 50.074 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Anti-factor Xa Values at Specified Time Points | Day 15: 2 to 4 hours post-dose | 99.415 microgram per liter (mcg/L) | Standard Deviation 54.415 |
Secondary
Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points
The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway.
Time frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Population: Pharmacodynamic analysis set (N=42) included all subjects with at least one blood sample for clotting parameters in accordance with the pharmacodynamic sampling strategy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 15: 2 to 4 hours post-dose | 10.982 seconds | Standard Deviation 4.47 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 15: 6 to 8 hours post-dose | 6.136 seconds | Standard Deviation 2.641 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA seconds | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 31: 20 to 24 hours post-dose | 1.345 seconds | Standard Deviation 3.19 |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 31: 20 to 24 hours post-dose | 1.240 seconds | Standard Deviation 4.992 |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 15: 2 to 4 hours post-dose | 12.818 seconds | Standard Deviation 5.21 |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA seconds | — |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 15: 6 to 8 hours post-dose | 5.900 seconds | Standard Deviation 4.942 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 31: 20 to 24 hours post-dose | NA seconds | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 15: 6 to 8 hours post-dose | 1.858 seconds | Standard Deviation 4.774 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 31: 10 to 16 hours post-dose | -0.483 seconds | Standard Deviation 6.488 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points | Day 15: 2 to 4 hours post-dose | 2.995 seconds | Standard Deviation 5.616 |
Secondary
Change From Baseline in Prothrombin Time at Specified Time Points
Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade.
Time frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Population: Pharmacodynamic analysis set (N=42) included all subjects with at least one blood sample for clotting parameters in accordance with the pharmacodynamic sampling strategy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 15: 2 to 4 hours post-dose | 8.964 seconds | Standard Deviation 3.822 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 15: 6 to 8 hours post-dose | 4.218 seconds | Standard Deviation 2.977 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA seconds | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 31: 20 to 24 hours post-dose | -0.082 seconds | Standard Deviation 1.02 |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 31: 20 to 24 hours post-dose | -0.327 seconds | Standard Deviation 1.332 |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 15: 2 to 4 hours post-dose | 9.083 seconds | Standard Deviation 2.513 |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA seconds | — |
| Comparator, Age: 12 - <18 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 15: 6 to 8 hours post-dose | 2.817 seconds | Standard Deviation 1.628 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 31: 20 to 24 hours post-dose | NA seconds | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 15: 6 to 8 hours post-dose | 1.984 seconds | Standard Deviation 1.341 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 31: 10 to 16 hours post-dose | 0.156 seconds | Standard Deviation 1.155 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Change From Baseline in Prothrombin Time at Specified Time Points | Day 15: 2 to 4 hours post-dose | 3.147 seconds | Standard Deviation 2.099 |
Secondary
Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points
Geometric and percentage geometric coefficient of variation (%CV) were reported.
Time frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Population: Pharmacokinetic analysis set (N= 42) included all subjects with at least one pharmacokinetic sample in accordance with the pharmacokinetic sampling strategy.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA microgram per liter (mcg/L) | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: 6 to 8 hours post-dose | 124.6723 microgram per liter (mcg/L) | Geometric Coefficient of Variation 49.1882 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: pre-dose | 20.4822 microgram per liter (mcg/L) | Geometric Coefficient of Variation 40.6726 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: 2 to 4 hours post-dose | 219.6933 microgram per liter (mcg/L) | Geometric Coefficient of Variation 35.7518 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 31: 20 to 24 hours post-dose | 21.3252 microgram per liter (mcg/L) | Geometric Coefficient of Variation 43.1274 |
| Comparator, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: 6 to 8 hours post-dose | 96.8051 microgram per liter (mcg/L) | Geometric Coefficient of Variation 41.8155 |
| Comparator, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: pre-dose | 7.4367 microgram per liter (mcg/L) | Geometric Coefficient of Variation 152.9768 |
| Comparator, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: 2 to 4 hours post-dose | 240.6319 microgram per liter (mcg/L) | Geometric Coefficient of Variation 18.3387 |
| Comparator, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 31: 10 to 16 hours post-dose | NA microgram per liter (mcg/L) | — |
| Comparator, Age: 12 - <18 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 31: 20 to 24 hours post-dose | 9.4654 microgram per liter (mcg/L) | Geometric Coefficient of Variation 167.7545 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 31: 20 to 24 hours post-dose | NA microgram per liter (mcg/L) | — |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 31: 10 to 16 hours post-dose | 43.5223 microgram per liter (mcg/L) | Geometric Coefficient of Variation 81.7283 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: pre-dose | 41.6025 microgram per liter (mcg/L) | Geometric Coefficient of Variation 183.6873 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: 6 to 8 hours post-dose | 100.5992 microgram per liter (mcg/L) | Geometric Coefficient of Variation 52.6497 |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points | Day 15: 2 to 4 hours post-dose | 119.2201 microgram per liter (mcg/L) | Geometric Coefficient of Variation 52.9889 |
Secondary
Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden
The occurrence of asymptomatic deterioration in thrombotic burden was summarized by age group. Asymptomatic deterioration in thrombotic burden was documented by the appropriate imaging test and the results were classified as normalized, improved, no relevant change, deteriorated, not evaluable or not available.
Time frame: Repeat imaging at the end of the 30 day treatment period
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Improved | 4 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not available | 4 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | No relevant change | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not evaluable | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Deteriorated | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Normalized | 3 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | No relevant change | 0 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not available | 9 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Improved | 0 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Normalized | 2 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Deteriorated | 0 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not evaluable | 2 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Deteriorated | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | No relevant change | 1 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Normalized | 2 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not evaluable | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not available | 2 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Improved | 8 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Deteriorated | 0 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Normalized | 4 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | No relevant change | 2 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not evaluable | 0 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not available | 4 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Improved | 9 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not available | 1 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Normalized | 1 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Improved | 4 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | No relevant change | 0 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Deteriorated | 0 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden | Not evaluable | 1 Participants |
Secondary
Number of Subjects With Symptomatic Recurrent Venous Thromboembolism
The occurrence of recurrent venous thromboembolism was summarized by age group. Symptomatic recurrence of venous thrombosis was documented by the appropriate imaging test.
Time frame: From start of study drug administration until end of the 30-day treatment period
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 12 - <18 Years | Number of Subjects With Symptomatic Recurrent Venous Thromboembolism | 0 Participants |
| Comparator, Age: 12 - <18 Years | Number of Subjects With Symptomatic Recurrent Venous Thromboembolism | 0 Participants |
| Rivaroxaban (BAY59-7939) Tablet, OD, Age: 6 - <12 Years | Number of Subjects With Symptomatic Recurrent Venous Thromboembolism | 0 Participants |
| Rivaroxaban (BAY59-7939) Suspension, BID, Age: 6 - <12 Years | Number of Subjects With Symptomatic Recurrent Venous Thromboembolism | 0 Participants |
| Comparator, Age: 6 - < 12 Years | Number of Subjects With Symptomatic Recurrent Venous Thromboembolism | 0 Participants |