Study to Compare the Effect of the Formulations (Orally Disintegrating Tablet and Film-coated Tablet) on Bioequivalence of Drug Rivaroxaban (Xarelto) at Dose of 10 mg in Japanese Healthy Male Adult Subjects

Bayer

Status and phase: Completed; Phase 1

Conditions: Clinical Pharmacology

Treatments: Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form; Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form

Study type: Interventional

Funder types: Industry

Identifiers

NCT04511611

20087

Details and patient eligibility

About

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 10 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 10 mg ODT either with or without water and one oral dose of rivaroxaban 10 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.

Enrollment: 80 patients

Sex: Male

Ages: 20 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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80 participants in 4 patient groups

Test A: 10 mg ODT with water, then 10 mg film-coated tablet

Experimental group

Description:

Participants received one single dose of 10 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 10 mg rivaroxaban film-coated tablet in the fasted state

Treatment:

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form

Test A: 10 mg film-coated tablet, then 10 mg ODT with water

Experimental group

Description:

Participants received one single dose of 10 mg rivaroxaban film-coated tablet in the fasted state. After a washing period of 5 days, participants received one single oral dose of 10 mg rivaroxaban orally disintegrating tablet (ODT) with water in the fasted state

Treatment:

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form

Test B: 10 mg ODT without water, then 10 film-coated tablet

Experimental group

Description:

Participants received one single dose of 10 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 10 mg rivaroxaban film-coated tablet in the fasted state

Treatment:

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form

Test B: 10 mg film-coated tablet, then 10 mg ODT without water

Experimental group

Description:

Participants received one single dose of 10 mg rivaroxaban film-coated tablet in the fasted state. After a washing period of 5 days, participants received one single oral dose of 10 mg rivaroxaban orally disintegrating tablet (ODT) without water in the fasted state

Treatment:

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form

Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form