Study to Compare the Effect of the Formulations (Orally Disintegrating Tablet and Film-coated Tablet) on the Bioequivalence of Drug Rivaroxaban (Xarelto) at Dose of 15 mg in Japanese Healthy Male Adult Subjects

Study Overview
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Brief Summary
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Researchers in this study wanted to compare the effect of the formulation (orally disintegrating tablet and film-coated tablet) on the bioequivalence of drug Rivaroxaban (brand name: Xarelto) at dose of 15 mg in Japanese healthy male subjects aged 20 to 40 years. Rivaroxaban is an approved drug to be used for the prevention of events/diseases caused by blood clots. Currently, there are two formulations of Rivaroxaban available on the market in Japan and they are film-coated tablets and fine granules. To further improve patients' convenience, a new formulation, orally disintegrating tablet (ODT, a drug dosage form designed to be dissolved on the tongue rather than swallowed whole) is under development. The goal of this study was to compare the effect of this new formulation with film-coated tablets when taken with or without water. Participants in this study received one oral dose of rivaroxaban 15 mg ODT either with or without water and one oral dose of rivaroxaban 15 mg film-tablet. There were at least 5 days between the two doses. Observation for each participant lasted about 6 weeks in total. Blood samples were collected from the participants to measure the blood level of the study drug.

Official Title
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Randomized, Non-blinded, Two-way Crossover Study to Assess Bioequivalence Between a Rivaroxaban 15 mg Orally Disintegrating Tablet Administered With Water or Without Water and a Rivaroxaban 15 mg Film-coated Tablet in Japanese Healthy Male Adult Subjects

Conditions
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Clinical Pharmacology

Intervention / Treatment
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* Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form
* Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese healthy male subjects, aged 20 to 40 years (inclusive), with body mass index 17.6 to 26.4 kg/m² Exclusion Criteria: Subject with 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 Subject with known hypersensitivity to the study drugs (active substances or excipients of the preparations) Subject with known coagulation disorders (e.g. von Willebrand disease, hemophilia) Subject with febrile illness within 1 week before the first study drug administration Subject with suspicion of drug or alcohol abuse Subject with intake of foods or beverages containing grapefruit, pomelo, Seville orange, and tangelo within 1 week before the first study drug administration Subject with therapies (e.g. physiotherapy, acupuncture, etc.) within 1 month before starting study treatment Subject with clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree atrioventricular block, prolongation of the QRS complex over 120 msec or of the corrected QT (QTc) interval over 450 msec Subject with systolic blood pressure below 90 or above 130 mmHg Subject with diastolic blood pressure below 45 or above 85 mmHg Subject with clinically relevant deviations of the screened laboratory parameters from reference ranges

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test C: 15 mg ODT with water, then 15 mg film-coated tablet<br>Participants received one single dose of 15 mg rivaroxaban orally disintegrating tablet (ODT) with water in the fasted state. After a washing period of 5 days, participants received one single oral dose of 15 mg rivaroxaban film-coated tablet in the fasted state | Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form<br>* 15 mg as 1 x 15 mg orally disintegrating tablet (ODT)<br>Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form<br>* 15 mg as 1 x 15 mg film-coated tablet<br>|
| Experimental: Test C: 15 mg film-coated tablet, then 15 mg ODT with water<br>Participants received one single dose of 15 mg rivaroxaban film-coated tablet in the fasted state. After a washing period of 5 days, participants received one single oral dose of 15 mg rivaroxaban orally disintegrating tablet (ODT) with water in the fasted state | Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form<br>* 15 mg as 1 x 15 mg orally disintegrating tablet (ODT)<br>Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form<br>* 15 mg as 1 x 15 mg film-coated tablet<br>|
| Experimental: Test D: 15 mg ODT without water, then 15 film-coated tablet<br>Participants received one single dose of 15 mg rivaroxaban orally disintegrating tablet (ODT) without water in the fasted state. After a washing period of 5 days, participants received one single oral dose of 15 mg rivaroxaban film-coated tablet in the fasted state | Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form<br>* 15 mg as 1 x 15 mg orally disintegrating tablet (ODT)<br>Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form<br>* 15 mg as 1 x 15 mg film-coated tablet<br>|
| Experimental: Test D: 15 mg film-coated tablet, then 15 mg ODT without water<br>Participants received one single dose of 15 mg rivaroxaban film-coated tablet in the fasted state. After a washing period of 5 days, participants received one single oral dose of 15 mg rivaroxaban orally disintegrating tablet (ODT) without water in the fasted state | Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form<br>* 15 mg as 1 x 15 mg orally disintegrating tablet (ODT)<br>Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form<br>* 15 mg as 1 x 15 mg film-coated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for plasma rivaroxaban concentration | Maximum observed concentration | Up to 48 hours after study medication | 
| AUC(0-tlast) for plasma rivaroxaban concentration | Area under the concentration versus time curve from time 0 to the last data point > lower limit of quantitation | Up to 48 hours after study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with treatment-emergent adverse events |  | Up to 30 days after study medication |