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

NCT04511611 | Completed Phase 1

• 1 other identifier: 20087
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Clinical Pharmacology

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Number of subjects with treatment-emergent adverse events

  Up to 30 days after study medication

Study Arms (4)

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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

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

Interventions

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

10 mg as 1 x 10 mg orally disintegrating tablet (ODT)

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

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

10 mg as 1 x 10 mg film-coated tablet

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

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- Japanese healthy male subjects, aged 20 to 40 years (inclusive), with body mass index 17.6 to 26.4 kg/m²

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (3)

Sumida Hospital

Sumida-ku, Tokyo, 130-0004, Japan

Location

Fukuoka Mirai Hospital

Fukuoka, 813-0017, Japan

Location

Medical Co. LTA Nishikumamoto hospital

Kumamoto, 861-4157, Japan

Location

Related Links

• Click here to find results for studies related to Bayer products

MeSH Terms

Interventions

Rivaroxaban

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 13, 2020
• Study Start: January 24, 2019
• Primary Completion: March 27, 2019
• Study Completion: May 13, 2019
• Last Updated: August 13, 2020

Record last verified: 2020-08

Locations

JP (3)