Relative Bioavailability of Oral Suspension of Rivaroxaban Compared to Standard Tablet

Study Overview
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Brief Summary
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Rivaroxaban is a substance developed for use in the treatment of blood coagulation disorders. Thrombosis (blood clots) can occur as a result of excessive coagulation activity in the blood vessels. Excessive coagulation activity can occur in children as well, and rivaroxaban is therefore being developed for the treatment of thromboembolic events in children and adolescents. As small children are often unable to swallow tablets, an oral suspension (mixture of a liquid containing finely distributed solids) has been developed which allows dosing according to body weight. The objective of this trial is to compare the bioavailability (proportion of a substance that remains available unchanged in the blood circulation) of a rivaroxaban oral solution with that of the rivaroxaban tablet approved for treatment. In order to evaluate the potential influence of food, the oral suspension containing 20 mg rivaroxaban will be taken after consuming food. In addition, the pharmacokinetics (concentrations of the drug and breakdown products (metabolites) in blood), safety and tolerability will be assessed.

Official Title
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Single-dose, Open-label, Randomized, 4-way Crossover Study to Compare 10 mg of an Oral Suspension of Rivaroxaban Under Fasting (2 Different Batches) and 20 mg of an Oral Suspension of Rivaroxaban Under Fed Conditions to 10 mg of an Immediate Release Tablet Under Fasting Conditions in Healthy Subjects

Conditions
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Biological Availability

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects Age: 18 to 55 years (inclusive) at the first screening examination Exclusion Criteria: Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal Known coagulation disorders (eg von Willebrand's disease, hemophilia) Known disorders with increased bleeding risk (eg periodontosis, hemorrhoids, acute gastritis, peptic ulcer) Known sensitivity to common causes of bleeding (eg nasal) Regular use of medicines Clinically relevant findings in the ECG (electrocardiogram) such as a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QTc-interval over 450 msec Clinically relevant findings in the physical examination Clinically relevant deviations of the screened laboratory parameters from reference ranges Participation in another clinical study during the preceding 3 months (Last Treatment from previous study to First Treatment of new study)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban (Treatment A) suspension (BN03501), fasted<br>Subjects received single oral dose of Rivaroxaban suspension 10 mg (Treatment A, Batch number BN03501) under fasting conditions in any intervention period. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br> <br> |
| Experimental: Rivaroxaban (Treatment B) suspension (BN03501), fed<br>Subjects received single oral dose of Rivaroxaban suspension 20 mg (Treatment B, Batch number BN03501) under fed conditions in any intervention period. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br> <br> |
| Experimental: Rivaroxaban (Treatment C) suspension (BR05701), fasted<br>Subjects received single oral dose of Rivaroxaban suspension 10 mg (Treatment C, Batch number BR05701) under fasting conditions in any intervention period. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br> <br> |
| Experimental: Rivaroxaban (Treatment D) IR tablet, fasted<br>Subjects received single oral dose of Rivaroxaban IR tablet 10 mg (Treatment D) under fasting conditions in any intervention period. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration Versus Time Curve From Zero to Infinity After a Single Dose (AUC) |  | 0-72 hours | 
| Area Under the Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) |  | 0-72 hours | 
| Maximum Observed Drug Concentration in Measured Matrix After a Single Dose (Cmax) |  | 0-72 hours | 
| Maximum Observed Drug Concentration in Measured Matrix Divided by Dose (Cmax/D) |  | 0-72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration Versus Time Curve From Zero to Infinity Divided by Dose per Kilogram Body Weight (AUC,norm) |  | 0-72 hours | 
| Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration [AUC(0tlast)] |  | 0-72 hours | 
| Maximum Observed Drug Concentration Divided by Dose per Kilogram Body Weight (Cmax,norm) |  | 0-72 hours | 
| Mean Residence Time (MRT) |  | 0-72 hours | 
| Maximum Observed Drug Concentration Divided by Drug Concentration at 24 hours (Cmax/C24h) |  | 0-72 hours | 
| Time to Reach Maximum Observed Drug Concentration (tmax) |  | 0-72 hours | 
| Terminal Half Life (t1/2) |  | 0-72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relative bioavailability, Rivaroxaban