Trial Outcomes & Findings for Bioequivalence Study in Healthy Subjects, 2*5 mg Tablets Rivaroxaban Versus 1*10 mg Tablet Rivaroxaban (NCT NCT01436526)

NCT ID: NCT01436526

Last Updated: 2015-04-22

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 28 participants
• Primary outcome 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
• Results posted on: 2015-04-22

Participant Flow

All participants (part.) recruited by CRS Clinical-Research-Services Moenchengladbach GmbH, Hindenburgstrasse 304 - 306, 41061 Moenchengladbach, Germany. 28 part. were planned to be enrolled.

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.

Participant milestones

Measure	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)	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)
Period 1 STARTED	14	14
Period 1 Participants Received Treatment	14	14
Period 1 COMPLETED	14	14
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	13	13
Period 2 Participants Received Treatment	13	13
Period 2 COMPLETED	13	13
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Rivaroxaban (Xarelto, BAY59-7939) First 2*5 mg , Then 1*10 mg n=14 Participants 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)	Rivaroxaban (Xarelto, BAY59-7939) First 1*10 mg, Then 2*5 mg n=14 Participants 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 n=28 Participants Total of all reporting groups
Age, Continuous	31.6 Years STANDARD_DEVIATION 5.8 • n=5 Participants	31.3 Years STANDARD_DEVIATION 10.5 • n=7 Participants	31.4 Years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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).

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity After Single Dose (AUC) Incl. Bioequivalence (BE) Evaluation	1374 µg*hr/L Geometric Coefficient of Variation 29.3	1268 µg*hr/L Geometric Coefficient of Variation 30.7

PRIMARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tn)] Incl. Bioequivalence (BE) Evaluation	1354 µg*hr/L Geometric Coefficient of Variation 29.8	1252 µg*hr/L Geometric Coefficient of Variation 31.6

PRIMARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Maximum Observed Drug Concentration in Plasma After Single Dose Administration (Cmax) Incl. Bioequivalence (BE) Evaluation	179.8 µg/L Geometric Coefficient of Variation 31.1	161.1 µg/L Geometric Coefficient of Variation 38.7

SECONDARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Area Under the Plasma Concentration Versus Time Curve Divided by Dose Per kg Body Weight (AUCnorm)	10.79 kg*hr/L Geometric Coefficient of Variation 33.0	9.957 kg*hr/L Geometric Coefficient of Variation 36.4

SECONDARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Maximum Observed Drug Concentration in Plasma After Single Dose Administration Divided by Dose Per kg Body Weight (Cmax, Norm)	1.412 kg/L Geometric Coefficient of Variation 35.3	1.265 kg/L Geometric Coefficient of Variation 46.0

SECONDARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Mean Residence Time (MRT)	8.874 hr Geometric Coefficient of Variation 22.0	9.284 hr Geometric Coefficient of Variation 28.2

SECONDARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Time to Reach Maximum Drug Concentration in Plasma After Single Dose (Tmax)	2.50 hr Interval 0.75 to 3.0	2.50 hr Interval 0.75 to 4.0

SECONDARY outcome

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

Population: N=26 valid for pharmacokinetic analysis

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.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 2*5 mg n=26 Participants Single oral dose of 2\*5 mg rivaroxaban tablet administered under fasting conditions	Rivaroxaban (Xarelto, BAY59-7939) 1*10 mg n=26 Participants Single oral dose of 1\*10 mg rivaroxaban tablets administered under fasting conditions
Half-life Associated With the Terminal Slope (t½)	8.932 hr Geometric Coefficient of Variation 48.6	8.721 hr Geometric Coefficient of Variation 55.7

Adverse Events

Rivaroxaban 2*5 mg (Xarelto, BAY59-7939)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Rivaroxaban 1*10 mg (Xarelto, BAY59-7939)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Rivaroxaban 2*5 mg (Xarelto, BAY59-7939) n=27 participants at risk Single oral dose of 2\*5 mg rivaroxaban tablets administered under fasting conditions	Rivaroxaban 1*10 mg (Xarelto, BAY59-7939) n=27 participants at risk Single oral dose of 1\*10 mg rivaroxaban tablet administered under fasting conditions
Cardiac disorders Sinus bradycardia	3.7% 1/27 • Number of events 1	3.7% 1/27 • Number of events 1
Gastrointestinal disorders Constipation	0.00% 0/27	3.7% 1/27 • Number of events 1
Gastrointestinal disorders Diarrhoea	0.00% 0/27	3.7% 1/27 • Number of events 1
Gastrointestinal disorders Dyspepsia	0.00% 0/27	3.7% 1/27 • Number of events 1
General disorders Fatigue	0.00% 0/27	3.7% 1/27 • Number of events 1
General disorders Injection site haematoma	0.00% 0/27	3.7% 1/27 • Number of events 1
Injury, poisoning and procedural complications Contusion	3.7% 1/27 • Number of events 1	0.00% 0/27
Investigations Alanine aminotransferase increased	3.7% 1/27 • Number of events 1	0.00% 0/27
Investigations Aspartate aminotransferase increased	3.7% 1/27 • Number of events 1	0.00% 0/27
Investigations Blood amylase increased	3.7% 1/27 • Number of events 1	0.00% 0/27
Investigations Lipase increased	3.7% 1/27 • Number of events 1	0.00% 0/27
Investigations Glutamate dehydrogenase increased	7.4% 2/27 • Number of events 2	0.00% 0/27
Nervous system disorders Headache	3.7% 1/27 • Number of events 1	0.00% 0/27
Renal and urinary disorders Haemoglobinuria	0.00% 0/27	3.7% 1/27 • Number of events 1
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.7% 1/27 • Number of events 1	0.00% 0/27

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any disclosure of study results by the Principal Investigator or investigators has to be in agreement with the sponsor.
• Publication restrictions are in place

Restriction type: OTHER