Bioequivalence Study in Healthy Subjects, 2*5 mg Tablets Rivaroxaban Versus 1*10 mg Tablet Rivaroxaban
This study has been completed.
Sponsor:
Bayer
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT01436526
First received: September 16, 2011
Last updated: March 21, 2013
Last verified: March 2013
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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
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: | Head Clinical Pharmacology, Bayer Healthcare AG |
| 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: | March 21, 2013 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Bayer:
|
Bioequivalence |
ClinicalTrials.gov processed this record on May 23, 2013