Relative Bioavailability Study in Healthy Subjects Comparing 2 Dry Powder Oral Suspensions of Rivaroxaban Under Fasting and 20 mg of an Oral Suspension of Rivaroxaban Under Fed Conditions to 10 mg of an Immediate Release Tablet Under Fasting Conditions

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 new oral suspension of rivaroxaban with a previously used oral suspension and with a rivaroxaban tablet approved for treatment. In order to evaluate the potential influence of food, the new 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 a Dry Powder Oral Suspension (10 mg and 20 mg Dose of Rivaroxaban) With an Oral Suspension (10 mg of Rivaroxaban) and 10 mg of an Immediate Release Tablet Under Fasting Conditions (10 mg Doses) and Under Fed Conditions (20 mg Dose) in Healthy Male Subjects

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* 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 White Body Mass Index (BMI): ≥18.0 and ≤29.9 kg/m2 at the screening visit. 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 (e.g. von Willebrand's disease, hemophilia) Known disorders with increased bleeding risk (e.g. periodontosis, hemorrhoids, acute gastritis, peptic ulcer) Known sensitivity to common causes of bleeding (e.g. nasal) Regular use of medicines and use of medication that may have an impact on the study objectives Clinically relevant findings in the ECG 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 - BAY59-7939<br>10 mg oral suspension (dry powder) in fasted conditions | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Single dose of 10 mg oral suspension (dry powder) in fasted conditions.<br>|
| Experimental: Arn 2 - BAY59-7939<br>20 mg oral suspension (dry powder) in fed conditions. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Single dose of 20 mg oral suspension (dry powder) in fed conditions.<br>|
| Experimental: Arm 3 - BAY59-7939<br>10 mg oral suspension in fasted conditions | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Single dose of 10 mg oral suspension in fasted conditions.<br>|
| Experimental: Arm 4 - BAY59-7939<br>10 mg tablet in fasted conditions. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Single dose of 10 mg tablet in fasted conditions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of rivaroxaban characterized by AUC | AUC:area under the concentration vs. time curve from zero to infinity after single (first) dose | Dosing day(15 min, 30 min ,45 min ,1 ,1.5, 2, 2.5 ,3 , 4, 6,8,12,15 hours), at 48 hr after administration), at 72 hr after administration) | 
| Plasma concentration of rivaroxaban characterized by AUC/D | AUC/D: AUC divided by dose | Dosing day(15 min, 30 min ,45 min ,1 ,1.5, 2, 2.5 ,3 , 4, 6,8,12,15 hours),at 48 hr after administration),at 72 hr after administration) | 
| Plasma concentration of rivaroxaban characterized by Cmax | Cmax: maximum drug concentration in plasma after single dose administration | Dosing day(15 min, 30 min ,45 min ,1 ,1.5, 2, 2.5 ,3 , 4, 6,8,12,15 hours),at 48 hr after administration),at 72 hr after administration) | 
| Plasma concentration of rivaroxaban characterized by Cmax/D | Cmax/D: Cmax divided by dose | Dosing day(15 min, 30 min ,45 min ,1 ,1.5, 2, 2.5 ,3 , 4, 6,8,12,15 hours),at 48 hr after administration),at 72 hr after administration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biological Availability, Relative Bioavailability Trial