Clinical trial NCT01436526: Bioequivalence Study in Healthy Subjects, 2*5 mg Tablets Rivaroxaban Versus 1*10 mg Tablet Rivaroxaban
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Therapeutic Equivalency
Keywords: Bioequivalence
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2011-09-19
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity After Single Dose (AUC) Incl. Bioequivalence (BE) Evaluation
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tn)] Incl. Bioequivalence (BE) Evaluation
timeFrame: 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
measure: Maximum Observed Drug Concentration in Plasma After Single Dose Administration (Cmax) Incl. Bioequivalence (BE) Evaluation
timeFrame: 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 outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve Divided by Dose Per kg Body Weight (AUCnorm)
timeFrame: 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
measure: Maximum Observed Drug Concentration in Plasma After Single Dose Administration Divided by Dose Per kg Body Weight (Cmax, Norm)
timeFrame: 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
measure: Mean Residence Time (MRT)
timeFrame: 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
measure: Time to Reach Maximum Drug Concentration in Plasma After Single Dose (Tmax)
timeFrame: 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
measure: Half-life Associated With the Terminal Slope (t½)
timeFrame: 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
Other outcomes:
Locations:
city: Mönchengladbach
country: Germany
state: Nordrhein-Westfalen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: