Trial Outcomes & Findings for Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A (NCT NCT01029340)

Last Updated: 2016-11-28

Results Overview

To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

74 participants

Primary outcome timeframe

Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity.

Results posted on

2016-11-28

Participant Flow

Participants were recruited from specialized hemophilia treatment centers.

14 participants were enrolled in each of Arms 1 and 2 in Part A. Of these, 11 participants continued into each of Arms 3 and 4 in Part B. Arm 3 enrolled 20 and Arm 4 enrolled 21 additional participants who had not participated in Part A. Arm 5 enrolled 5 participants specifically for surgery in Part C who had not participated in Parts A or B.

Participant milestones

Participant milestones
Measure	Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between	Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973) Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between	Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted (CS/ADJ) to Label Potency for 6 months	Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted (CS/ADJ) to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia (CS/EP) for 6 months	Arm 5: Recombinant Factor VIII by CS/EP Part C - Arm 5: Participants received a loading dose of approximately 50 IU/kg of BAY81-8973 before the first surgical incision followed by further treatment with BAY81-8973 according to surgical requirements for up to 3 weeks	Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension Participants received IV injections of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and CS/ADJ for 6 months sequence according to randomization and up to 12 months (CS/EP) during extension
Part A Treatment Period STARTED	14	14	0	0	0	0
Part A Treatment Period Participants Received Treatment	14	14	0	0	0	0
Part A Treatment Period Safety Population	13	14	0	0	0	0
Part A Treatment Period COMPLETED	14	14	0	0	0	0
Part A Treatment Period NOT COMPLETED	0	0	0	0	0	0
Part A Follow up Period STARTED	14	14	0	0	0	0
Part A Follow up Period COMPLETED	14	14	0	0	0	0
Part A Follow up Period NOT COMPLETED	0	0	0	0	0	0
Part B Treatment Period STARTED	0	0	31	32	0	0
Part B Treatment Period Participants Received Treatment	0	0	30	32	0	0
Part B Treatment Period COMPLETED	0	0	29	32	0	0
Part B Treatment Period NOT COMPLETED	0	0	2	0	0	0
Part B Follow up Period STARTED	0	0	29	32	0	0
Part B Follow up Period COMPLETED	0	0	29	32	0	0
Part B Follow up Period NOT COMPLETED	0	0	0	0	0	0
Extension Period STARTED	0	0	0	0	0	55
Extension Period COMPLETED	0	0	0	0	0	43
Extension Period NOT COMPLETED	0	0	0	0	0	12
Part C Treatment Period STARTED	0	0	0	0	5	0
Part C Treatment Period Participants Received Treatment	0	0	0	0	5	0
Part C Treatment Period COMPLETED	0	0	0	0	5	0
Part C Treatment Period NOT COMPLETED	0	0	0	0	0	0
Part C Follow up Period STARTED	0	0	0	0	5	0
Part C Follow up Period COMPLETED	0	0	0	0	5	0
Part C Follow up Period NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted (CS/ADJ) to Label Potency for 6 months	Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension Participants received IV injections of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and CS/ADJ for 6 months sequence according to randomization and up to 12 months (CS/EP) during extension
Part B Treatment Period Withdrawal by Subject	1	0
Part B Treatment Period Protocol Violation	1	0
Extension Period Adverse Event	0	1
Extension Period starting another study	0	8
Extension Period non-compliance	0	1
Extension Period Withdrawal by Subject	0	1
Extension Period Physician Decision	0	1

Baseline Characteristics

Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS n=14 Participants Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between	Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973) n=14 Participants Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between	Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ n=20 Participants Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months	Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP n=21 Participants Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia for 6 months	Arm 5: Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C n=5 Participants Participants received a loading dose of approximately 50 IU/kg of BAY81-8973 before the first surgical incision, followed by further treatment with BAY81-8973 according to surgical requirements for up to 3 weeks	Total n=74 Participants Total of all reporting groups
Age, Customized Part A < 18 years	1 Participants n=5 Participants	4 Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Age, Customized Part A =/> 18 years	12 Participants n=5 Participants	9 Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Age, Customized Part B < 18 years	NA Participants n=5 Participants	NA Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Age, Customized Part B =/> 18 years	NA Participants n=5 Participants	NA Participants n=7 Participants	25 Participants n=5 Participants	27 Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Age, Customized Part C < 18 years	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	0 Participants n=21 Participants	NA Participants n=10 Participants
Age, Customized Part C =/> 18 years	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	5 Participants n=21 Participants	NA Participants n=10 Participants
Sex/Gender, Customized Part A - Female	0 Participants n=5 Participants	0 Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Sex/Gender, Customized Part A - Male	13 Participants n=5 Participants	13 Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Sex/Gender, Customized Part B - Female	NA Participants n=5 Participants	NA Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Sex/Gender, Customized Part B - Male	NA Participants n=5 Participants	NA Participants n=7 Participants	30 Participants n=5 Participants	32 Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Sex/Gender, Customized Part C - Female	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	0 Participants n=21 Participants	NA Participants n=10 Participants
Sex/Gender, Customized Part C - Male	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	5 Participants n=21 Participants	NA Participants n=10 Participants
Most recent treatment before enrolment in the study On-demand	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants
Most recent treatment before enrolment in the study Prophylaxis	10 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants	24 Participants n=4 Participants	NA Participants n=21 Participants	NA Participants n=10 Participants

PRIMARY outcome

Timeframe: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity.

Population: PK Analysis Population

To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=26 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A n=26 Participants Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part A - Area Under the Drug Concentration-time Curve (AUC)	1889.23 Int.units x hours/deciliters (IU*h/dL) Geometric Coefficient of Variation 36.11	1583.91 Int.units x hours/deciliters (IU*h/dL) Geometric Coefficient of Variation 39.89

PRIMARY outcome

Timeframe: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.

Population: PK Analysis Population

To examine the PK characteristics of BAY81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=26 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A n=26 Participants Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part A - Half-life (t 1/2)	13.77 Hours (h) Geometric Coefficient of Variation 28.00	12.00 Hours (h) Geometric Coefficient of Variation 28.20

PRIMARY outcome

Timeframe: 12 months after randomization

Population: Intent to treat (ITT)

The annualized number of bleeds experienced by participants

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=62 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Annualized Number of Total Bleeds	1.03 Bleeds Interval 0.0 to 5.09	—

SECONDARY outcome

Timeframe: 15-30 minutes after the injection

Population: ITT. 1 measurement was taken in all participants at the start of the CS/EP labelled treatment period (CS/ADJ labelled treatment was experimental and will not be used for the future commercial drug, so no measurements were taken). Note: Only 59 of the 62 participants had valid recovery data.

The amount of Factor VIII found in blood samples taken after the injection of the study drug at the beginning of the CS/EP treatment period.

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=59 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)	2.50 Kg/dL Interval 2.09 to 2.77	—

SECONDARY outcome

Timeframe: 6 months on each potency

Population: ITT. Note: One participant in Part B did not receive any Recombinant Factor VIII measured by the CS/ADJ method, leading to 61 participants (not 62) in that group.

The annualized number of bleeds experienced by participants in each of the two treatment periods

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=62 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A n=61 Participants Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period	1.9 Bleeds Interval 0.0 to 4.4	1.9 Bleeds Interval 0.0 to 7.3

SECONDARY outcome

Timeframe: 6 months on each potency

Population: ITT. Note: One participant in Part B did not receive any Recombinant Factor VIII measured by the CS/ADJ method, leading to 61 participants (not 62) in that group.

The number of injections needed by participants to stop a bleed

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=108 Bleeds Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A n=128 Bleeds Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed	1.0 Injections Interval 0.0 to 11.0	1.0 Injections Interval 1.0 to 48.0

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: ITT. Note: Only 51 of the 62 participants had data available for the 12-month QoL analysis.

A measure of how treatment with BAY81-8973 affected the daily life of participants. the scoring system has 100 points. 0 is the worst possible score. 100 is the best possible score. Positive changes from baseline indicate an improvement in quality of life and negative changes indicate a deterioration.

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=51 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire	2.02 Scores on a scale Interval -22.9 to 26.5	—

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: ITT. Note: Only 61 of the 62 participants had data available for the Utility Index of the EQ-5D questionnaire at Month 12.

A measure of how treatment with BAY81-8973 affected the daily life of participants. 1.0 = Best possible score, -0.594 = Worst possible score. Positive changes from baseline indicate an improvement and negative changes indicate a deterioration.

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=61 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire	0.00 Scores on a scale Interval -0.6 to 0.5	—

SECONDARY outcome

Timeframe: Up to 6 weeks after first injection of study drug

Population: Safety population

A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=28 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part A - Number of Participants With Inhibitory Antibody Formation	0 Participants	—

SECONDARY outcome

Timeframe: Up to 12 months after drug administration

Population: Safety population

A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=62 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Number of Participants With Incidence of Inhibitory Antibody Formation	0 Participants	—

SECONDARY outcome

Timeframe: before and 3 weeks after surgery

Population: ITT

A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=5 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part C - Number of Participants With Incidence of Inhibitory Antibody Formation	0 Participants	—

SECONDARY outcome

Timeframe: Up to 6 weeks after drug administration

Population: Safety population

A test to analyze the formation of antibodies to HSP-70

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=28 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	0 Participants	—

SECONDARY outcome

Timeframe: Up to 12 months after drug administration

Population: ITT

A test to analyze the formation of antibodies to HSP-70

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=62 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	1 Participants	—

SECONDARY outcome

Timeframe: before and 3 weeks after surgery

Population: ITT

A test to analyze the formation of antibodies to HSP-70

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=5 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	0 Participants	—

SECONDARY outcome

Timeframe: Up to 4 weeks after drug administration

Population: ITT

A test to ensure that participants have not developed antibodies to HCP during the study

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=26 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	0 Participants	—

SECONDARY outcome

Timeframe: Up to 12 months after drug administration

Population: ITT

A test to ensure that participants have not developed antibodies to HCP during the study

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=62 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	0 Participants	—

SECONDARY outcome

Timeframe: before and 3 weeks after surgery

Population: ITT

A test to ensure that participants have not developed antibodies to HCP during the study

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=5 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	0 Participants	—

SECONDARY outcome

Timeframe: An average of 1 month after start of treatment

Population: ITT

An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=5 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery Excellent	1 Participants	—
Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery Good	4 Participants	—
Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery Moderate	0 Participants	—
Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery Poor	0 Participants	—

SECONDARY outcome

Timeframe: at the time of surgery

Population: ITT

An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations

Outcome measures

Outcome measures
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=5 Participants Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg
Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery Excellent	1 Participants	—
Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery Good	4 Participants	—
Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery Moderate	0 Participants	—
Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery Poor	0 Participants	—

Adverse Events

Recombinant Factor VIII (BAY81-8973) - Part A

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Kogenate FS (BAY14-2222) - Part A

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Recombinant Factor VIII (BAY81-8973) Part B and Extension

Serious events: 12 serious events

Other events: 43 other events

Deaths: 0 deaths

Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=27 participants at risk Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A n=28 participants at risk Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg	Recombinant Factor VIII (BAY81-8973) Part B and Extension n=62 participants at risk Participants received IV injections of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and CS/ADJ for 6 months sequence according to randomization and up to 12 months (CS/EP) during extension	Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C n=7 participants at risk Participants in Part C received a loading dose of approximately 50 IU/kg of BAY81-8973 (nearest whole vial amount) for less than 15 minutes before the first surgical incision. Then they received further treatment with BAY81-8973 according to surgical requirements up to 3 weeks.
Cardiac disorders Acute myocardial infarction	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Gastrointestinal disorders Ascites	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
General disorders Chest pain	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	3.2% 2/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
General disorders Spinal pain	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Infections and infestations Erysipelas	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Injury, poisoning and procedural complications Injury	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Musculoskeletal and connective tissue disorders Compartment syndrome	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Nervous system disorders Epilepsy	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Nervous system disorders Loss of consciousness	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Pregnancy, puerperium and perinatal conditions Cephalhaematoma	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Psychiatric disorders Suicidal ideation	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Psychiatric disorders Somatoform disorder	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Social circumstances Miscarriage of partner	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.

Other adverse events
Measure	Recombinant Factor VIII (BAY81-8973) - Part A n=27 participants at risk Participants received one single intravenous (IV) injection of BAY81-8973 50 IU/kg	Kogenate FS (BAY14-2222) - Part A n=28 participants at risk Participants received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg	Recombinant Factor VIII (BAY81-8973) Part B and Extension n=62 participants at risk Participants received IV injections of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and CS/ADJ for 6 months sequence according to randomization and up to 12 months (CS/EP) during extension	Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C n=7 participants at risk Participants in Part C received a loading dose of approximately 50 IU/kg of BAY81-8973 (nearest whole vial amount) for less than 15 minutes before the first surgical incision. Then they received further treatment with BAY81-8973 according to surgical requirements up to 3 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Blood and lymphatic system disorders Thymus disorder	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Gastrointestinal disorders Dental caries	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	6.5% 4/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Gastrointestinal disorders Diarrhoea	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	6.5% 4/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	28.6% 2/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Gastrointestinal disorders Dyspepsia	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Gastrointestinal disorders Nausea	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	6.5% 4/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Gastrointestinal disorders Vomiting	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	6.5% 4/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
General disorders Chest pain	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	6.5% 4/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
General disorders Pyrexia	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	1.6% 1/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	28.6% 2/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Infections and infestations Influenza	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	9.7% 6/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Infections and infestations Nasopharyngitis	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	22.6% 14/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Infections and infestations Pharyngitis	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	8.1% 5/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Infections and infestations Upper respiratory tract infection	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	3.6% 1/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	12.9% 8/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Infections and infestations Device related infection	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	9.7% 6/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	6.5% 4/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Renal and urinary disorders Anuria	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	8.1% 5/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Respiratory, thoracic and mediastinal disorders Pulmonary artery dilatation	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	14.3% 1/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.
Vascular disorders Hypertension	0.00% 0/27 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/28 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	8.1% 5/62 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.	0.00% 0/7 • From the date of signing informed consent through study completion, i.e. 21 Dec 2009 to 14 Mar 2013 The objective of Part C was efficacy assessment of surgery hemostasis, not safety assessment. It was allowed to include the same patient for several surgeries and for each surgery the patient was assigned a new patient number. Due to this approach, one patient with 3 surgeries was analyzed as 3 different patients, therefore the number at risk is 7.