Bioequivalence Study in Healthy Subjects, 2*5 mg Tablets Rivaroxaban Versus 1*10 mg Tablet Rivaroxaban

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01436526
First received: September 16, 2011
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The drug investigated in this study is Rivaroxaban, a novel, once-daily, oral anticoagulant for the prevention (prophylaxis) of deep vein thrombosis (DVT) which may lead to a pulmonary embolism (PE) in people undergoing knee or hip replacement surgery.

The purpose of this study is to establish bioequivalence of 2 immediate-release tablet treatments with Rivaroxaban: 2*5 mg tablets and 1*10 mg tablet will be given to healthy volunteers under fasting conditions; they will be administered as single oral doses in 2 periods. Both periods will be separated by a 7-day washout phase. Thus, the bioequivalence represents the primary study objective. As a secondary objective, this treatment will be assessed in terms of safety and tolerability.

Bioequivalence will be evaluated and verified on the basis of pharmacokinetic data. Blood samples of the volunteers will be taken at specific points in time; these samples will be analyzed using various statistical methods to establish pharmacokinetic characteristics required to compare the 2 treatments. The planned treatments with Rivaroxaban will be considered bioequivalent if specific criteria defined in the study protocol are met.

The study will be conducted in one center in Germany. 28 subjects meeting the inclusion criteria will participate. They will be treated according to a single-dose, randomized, 2-way cross-over, non-placebo-controlled design.


Condition Intervention Phase
Therapeutic Equivalency
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Single-dose, Open-label, Randomized, 2-way Crossover Pivotal Bioequivalence Study of 2x5 mg Tablets Rivaroxaban Versus 1x10 mg Tablet Rivaroxaban Under Fasted Condition in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity After Single Dose (AUC) Incl. Bioequivalence (BE) Evaluation [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample (AUC is defined as area under the concentration vs. time curve from zero to infinity after single (first) dose).

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tn)] Incl. Bioequivalence (BE) Evaluation [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; [AUC (0-tn)] is defined as AUC from time 0 to the last data point above the Lower Limit of Quantification.

  • Maximum Observed Drug Concentration in Plasma After Single Dose Administration (Cmax) Incl. Bioequivalence (BE) Evaluation [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.


Secondary Outcome Measures:
  • Area Under the Plasma Concentration Versus Time Curve Divided by Dose Per kg Body Weight (AUCnorm) [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; AUCnorm is defined as AUC divided by dose per kg body weight.

  • Maximum Observed Drug Concentration in Plasma After Single Dose Administration Divided by Dose Per kg Body Weight (Cmax, Norm) [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; Cmax,norm is defined as Cmax divided by dose (mg) per kg body weight.

  • Mean Residence Time (MRT) [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    The mean residence time is the average time that the molecules introduced into the body stay in the body.

  • Time to Reach Maximum Drug Concentration in Plasma After Single Dose (Tmax) [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.

  • Half-life Associated With the Terminal Slope (t½) [ Time Frame: 0 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours, 24 hours, 36 hours, 48 hours and 72 hours post administration ] [ Designated as safety issue: No ]
    Half-life refers to the elimination of the drug, i.e. the time it takes for the blood plasma concentration to reach half the concentration in the terminal phase of elimination.


Enrollment: 28
Study Start Date: August 2009
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban (Xarelto, BAY59-7939) first 2*5 mg, then 1*10 mg
Single oral dose of rivaroxaban administered under fasting conditions 2*5 mg tablet in first intervention period and 1*10 mg tablet in second intervention period (after washout period)
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Single oral dose of rivaroxaban administered under fasting conditions 2*5 mg tablet in first intervention period and 1*10 mg tablet in second intervention period (after washout period)
Experimental: Rivaroxaban (Xarelto, BAY59-7939) first 1*10 mg, then 2*5 mg
Single oral dose of rivaroxaban administered under fasting conditions 1*10 mg tablet in first intervention period and 2*5 mg tablet in second intervention period (after washout period)
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Single oral dose of rivaroxaban administered under fasting conditions 1*10 mg tablet in first intervention period and 2*5 mg tablet in second intervention period (after washout period)

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male subjects
  • 18 to 45 years of age
  • Body mass index (BMI) between 18 and 30 kg/m2

Exclusion Criteria:

  • Conspicuous findings (medical history, screening)
  • History of relevant diseases (internal organs, central nervous system or other organs)
  • Medical disorder, condition or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator or the sponsor
  • Febrile illness within 1 week before the start of the study
  • History of severe allergies, non-allergic drug reactions, or multiple drug allergies
  • Hypersensitivity to the investigational drug, the control agent and/or to inactive constituents
  • Known coagulation disorders, known disorders with increased bleeding risk, known sensitivity to common causes of bleeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01436526

Locations
Germany
Mönchengladbach, Nordrhein-Westfalen, Germany, 41061
Sponsors and Collaborators
Bayer
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01436526     History of Changes
Other Study ID Numbers: 14588, 2009-013032-20
Study First Received: September 16, 2011
Results First Received: November 18, 2011
Last Updated: April 2, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Bioequivalence

Additional relevant MeSH terms:
Rivaroxaban
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014