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

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01436526
• Collaborator: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 27.5

Study Details

Study Description

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: 25 mg tablets and 110 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 or Disease	Intervention/Treatment	Phase
Therapeutic Equivalency	Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (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
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

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)
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)

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity After Single Dose (AUC) Incl. Bioequivalence (BE) Evaluation [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]

   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).

2. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tn)] Incl. Bioequivalence (BE) Evaluation [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]

   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.

3. Maximum Observed Drug Concentration in Plasma After Single Dose Administration (Cmax) Incl. Bioequivalence (BE) Evaluation [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]

   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

1. Area Under the Plasma Concentration Versus Time Curve Divided by Dose Per kg Body Weight (AUCnorm) [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]

   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.

2. Maximum Observed Drug Concentration in Plasma After Single Dose Administration Divided by Dose Per kg Body Weight (Cmax, Norm) [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]

   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.

3. Mean Residence Time (MRT) [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]

   The mean residence time is the average time that the molecules introduced into the body stay in the body.

4. Time to Reach Maximum Drug Concentration in Plasma After Single Dose (Tmax) [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]

   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.

5. Half-life Associated With the Terminal Slope (t½) [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 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1		Mönchengladbach	Nordrhein-Westfalen	Germany	41061

Sponsors and Collaborators

• Bayer
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT01436526
• Other Study ID Numbers: 14588; 2009-013032-20
• First Posted: Sep 19, 2011
• Last Update Posted: Apr 22, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Bayer: Bioequivalence
• Additional relevant MeSH terms: Rivaroxaban

Study Results

Participant Flow

Recruitment Details	All participants (part.) recruited by CRS Clinical-Research-Services Moenchengladbach GmbH, Hindenburgstrasse 304 - 306, 41061 Moenchengladbach, Germany. 28 part. were planned to be enrolled.
Pre-assignment Detail	37 participants screened; 9 participants were screening failures; 28 participants were included in the study. Safety analysis: 27 individuals were analyzed in the group with 2*5mg, 27 individuals were analyzed in the group with 1*10mg.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) First 2*5 mg, Then 1*10 mg	Rivaroxaban (Xarelto, BAY59-7939) First 1*10 mg, Then 2*5 mg
Arm/Group Description	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)	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)
Period Title: Period 1
STARTED	14	14
Participants Received Treatment	14	14
COMPLETED	14	14
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	13	13
Participants Received Treatment	13	13
COMPLETED	13	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) First 2*5 mg , Then 1*10 mg	Rivaroxaban (Xarelto, BAY59-7939) First 1*10 mg, Then 2*5 mg	Total
Arm/Group Description	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)	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)	Total of all reporting groups
Overall Participants	14	14	28
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.6 (5.8)	31.3 (10.5)	31.4 (8.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	14 100%	14 100%	28 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity After Single Dose (AUC) Incl. Bioequivalence (BE) Evaluation
Description	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).
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [µg*hr/L]	1374 (29.3)	1268 (30.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg, Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Using an estimated intra-subject coefficient of variation of less than 20% for AUC and Cmax, and a level of significance of 5%, a sample size of 25 completers was considered sufficient to conclude bioequivalence between 2*5 mg and 1*10 mg rivaroxaban with 90% power, if the 2 treatment means differed by 5%.
Statistical Test of Hypothesis	p-Value	0.0438
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS-Mean Ratio, Percent
	Estimated Value	108.35
	Confidence Interval	() 90%; 101.59 to 115.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tn)] Incl. Bioequivalence (BE) Evaluation
Description	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.
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [µg*hr/L]	1354 (29.8)	1252 (31.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg, Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Using an estimated intra-subject coefficient of variation of less than 20% for AUC and Cmax, and a level of significance of 5%, a sample size of 25 completers was considered sufficient to conclude bioequivalence between 2*5 mg and 1*10 mg rivaroxaban with 90% power, if the 2 treatment means differed by 5%.
Statistical Test of Hypothesis	p-Value	0.0514
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS-Mean Ratio, Percent
	Estimated Value	108.19
	Confidence Interval	() 90%; 101.31 to 115.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Maximum Observed Drug Concentration in Plasma After Single Dose Administration (Cmax) Incl. Bioequivalence (BE) Evaluation
Description	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.
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [µg/L]	179.8 (31.1)	161.1 (38.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg, Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Using an estimated intra-subject coefficient of variation of less than 20% for AUC and Cmax, and a level of significance of 5%, a sample size of 25 completers was considered sufficient to conclude bioequivalence between 2*5 mg and 1*10 mg rivaroxaban with 90% power, if the 2 treatment means differed by 5%.
Statistical Test of Hypothesis	p-Value	0.0685
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS-Mean Ratio, Percent
	Estimated Value	111.64
	Confidence Interval	() 90%; 101.14 to 123.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve Divided by Dose Per kg Body Weight (AUCnorm)
Description	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.
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [kg*hr/L]	10.79 (33.0)	9.957 (36.4)

5. Secondary Outcome

Title	Maximum Observed Drug Concentration in Plasma After Single Dose Administration Divided by Dose Per kg Body Weight (Cmax, Norm)
Description	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.
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [kg/L]	1.412 (35.3)	1.265 (46.0)

6. Secondary Outcome

Title	Mean Residence Time (MRT)
Description	The mean residence time is the average time that the molecules introduced into the body stay in the body.
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [hr]	8.874 (22.0)	9.284 (28.2)

7. Secondary Outcome

Title	Time to Reach Maximum Drug Concentration in Plasma After Single Dose (Tmax)
Description	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.
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Median (Full Range) [hr]	2.50	2.50

8. Secondary Outcome

Title	Half-life Associated With the Terminal Slope (t½)
Description	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.
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

Outcome Measure Data

Analysis Population Description

N=26 valid for pharmacokinetic analysis

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablet administered under fasting conditions	Single oral dose of 1*10 mg rivaroxaban tablets administered under fasting conditions
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [hr]	8.932 (48.6)	8.721 (55.7)

Adverse Events

Arm/Group Title	Rivaroxaban 2*5 mg (Xarelto, BAY59-7939)		Rivaroxaban 1*10 mg (Xarelto, BAY59-7939)
Arm/Group Description	Single oral dose of 2*5 mg rivaroxaban tablets administered under fasting conditions		Single oral dose of 1*10 mg rivaroxaban tablet administered under fasting conditions
All Cause Mortality
	Rivaroxaban 2*5 mg (Xarelto, BAY59-7939)		Rivaroxaban 1*10 mg (Xarelto, BAY59-7939)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rivaroxaban 2*5 mg (Xarelto, BAY59-7939)		Rivaroxaban 1*10 mg (Xarelto, BAY59-7939)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Rivaroxaban 2*5 mg (Xarelto, BAY59-7939)		Rivaroxaban 1*10 mg (Xarelto, BAY59-7939)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/27 (22.2%)		6/27 (22.2%)
Cardiac disorders
Sinus bradycardia	1/27 (3.7%)	1	1/27 (3.7%)	1
Gastrointestinal disorders
Constipation	0/27 (0%)	0	1/27 (3.7%)	1
Diarrhoea	0/27 (0%)	0	1/27 (3.7%)	1
Dyspepsia	0/27 (0%)	0	1/27 (3.7%)	1
General disorders
Fatigue	0/27 (0%)	0	1/27 (3.7%)	1
Injection site haematoma	0/27 (0%)	0	1/27 (3.7%)	1
Injury, poisoning and procedural complications
Contusion	1/27 (3.7%)	1	0/27 (0%)	0
Investigations
Alanine aminotransferase increased	1/27 (3.7%)	1	0/27 (0%)	0
Aspartate aminotransferase increased	1/27 (3.7%)	1	0/27 (0%)	0
Blood amylase increased	1/27 (3.7%)	1	0/27 (0%)	0
Lipase increased	1/27 (3.7%)	1	0/27 (0%)	0
Glutamate dehydrogenase increased	2/27 (7.4%)	2	0/27 (0%)	0
Nervous system disorders
Headache	1/27 (3.7%)	1	0/27 (0%)	0
Renal and urinary disorders
Haemoglobinuria	0/27 (0%)	0	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/27 (3.7%)	1	0/27 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any disclosure of study results by the Principal Investigator or investigators has to be in agreement with the sponsor.