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

• ClinicalTrials.gov Identifier: NCT04511637
• Recruitment Status: Completed
• First Posted: August 13, 2020
• Last Update Posted: August 13, 2020
• Sponsor: Bayer
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: August 12, 2020
• First Posted Date: August 13, 2020
• Last Update Posted Date: August 13, 2020
• Actual Study Start Date: January 21, 2019
• Actual Primary Completion Date: March 7, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2020)

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures (submitted: August 12, 2020): Number of subjects with treatment-emergent adverse events [ Time Frame: Up to 30 days after study medication ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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

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 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Clinical Pharmacology

Intervention

• Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form
  15 mg as 1 x 15 mg orally disintegrating tablet (ODT)
• Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form
  15 mg as 1 x 15 mg film-coated tablet

Study Arms

• Experimental: Test C: 15 mg ODT with water, then 15 mg film-coated tablet
  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
  Interventions:

  • Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form
  • Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form
• Experimental: Test C: 15 mg film-coated tablet, then 15 mg ODT with water
  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
  Interventions:

  • Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form
  • Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form
• Experimental: Test D: 15 mg ODT without water, then 15 film-coated tablet
  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
  Interventions:

  • Drug: Rivaroxaban (BAY 59-7939, Xarelto) in ODT form
  • Drug: Rivaroxaban (BAY 59-7939, Xarelto) in film-coated form
• Experimental: Test D: 15 mg film-coated tablet, then 15 mg ODT without water
  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
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 12, 2020): 80
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: April 12, 2019
• Actual Primary Completion Date: March 7, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 20 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04511637
• Other Study ID Numbers: 20088
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Janssen Research & Development, LLC
• Investigators: Not Provided
• PRS Account: Bayer
• Verification Date: August 2020