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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

September 16, 2011
April 2, 2014
August 2009
September 2009   (final data collection date for primary outcome measure)
  • 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.
  • 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 ]
  • 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 ]
  • 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 ]
Complete list of historical versions of study NCT01436526 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Therapeutic Equivalency
  • 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 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)
    Intervention: Drug: Rivaroxaban (Xarelto, BAY59-7939)
  • 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)
    Intervention: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
September 2009
September 2009   (final data collection date for primary outcome measure)

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
Male
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01436526
14588, 2009-013032-20
No
Bayer
Bayer
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study Director: Bayer Study Director Bayer
Bayer
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP