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

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

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.

Study Overview

• Status: Completed
• Conditions: Therapeutic Equivalency
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939)

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Mönchengladbach, Nordrhein-Westfalen, Germany, 41061

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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); 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)
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 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 1*10 mg tablet in first intervention period and 2*5 mg tablet in second intervention period (after washout period)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity After Single Dose (AUC) Incl. Bioequivalence (BE) Evaluation	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).	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
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tn)] Incl. Bioequivalence (BE) Evaluation	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.	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
Maximum Observed Drug Concentration in Plasma After Single Dose Administration (Cmax) Incl. Bioequivalence (BE) Evaluation	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve Divided by Dose Per kg Body Weight (AUCnorm)	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.	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
Maximum Observed Drug Concentration in Plasma After Single Dose Administration Divided by Dose Per kg Body Weight (Cmax, Norm)	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.	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
Mean Residence Time (MRT)	The mean residence time is the average time that the molecules introduced into the body stay in the body.	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
Time to Reach Maximum Drug Concentration in Plasma After Single Dose (Tmax)	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.	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
Half-life Associated With the Terminal Slope (t½)	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.	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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: September 16, 2011
• First Submitted That Met QC Criteria: September 16, 2011
• First Posted (Estimate): September 19, 2011

Study Record Updates

• Last Update Posted (Estimate): April 22, 2015
• Last Update Submitted That Met QC Criteria: April 2, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Bioequivalence
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 14588; 2009-013032-20 (EudraCT Number)