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Trial record 39 of 460 for:    Inherited Bleeding Disorder

A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A (PROTECT-VIII)

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ClinicalTrials.gov Identifier: NCT01580293
Recruitment Status : Active, not recruiting
First Posted : April 19, 2012
Results First Posted : December 6, 2018
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Intervention Biological: BAY94-9027
Enrollment 145
Recruitment Details The study was conducted in 3 parts: Part A (main study [36-week treatment period] and an optional extension [at least 100 total exposure days]) and Part B for major surgeries (up to 3 weeks).
Pre-assignment Details Of 149 participants screened in Part A, 134 were treated, reasons for non-inclusion were screen failure, consent withdrawal, and non-adherence to protocol visit windows. Participants selected either on-demand or prophylaxis treatment at start of study according to their preference. Randomization to prophylaxis arms occurred after week 10.
Arm/Group Title BAY94-9027 On-demand Treatment, Part A BAY94-9027 Prophylaxis Treatment, Part A BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description Participants received on-demand treatment with BAY94-9027 as an intravenous (IV) infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]). Participants entering extension either continued their on-demand treatment or switched to one of the prophylaxis regimens. All participants started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group). Participants entering extension either continued their prophylaxis regimen or switched to one of the other prophylaxis regimens. Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Period Title: Part A_Main Trial
Started [1] 20 114 0 [2]
Completed 18 108 0
Not Completed 2 6 0
Reason Not Completed
Adverse Event             0             2             0
Withdrawal by Subject             1             4             0
Non-adherence to the protocol             1             0             0
[1]
Received Treatment
[2]
Participants in Part B were not counted for Part A
Period Title: Part A_Extension
Started 14 [1] 107 [1] 0 [2]
Extension Ongoing 9 69 0
Completed 5 32 0
Not Completed 9 75 0
Reason Not Completed
Adverse Event             0             2             0
Withdrawal by Subject             0             2             0
Lost to Follow-up             0             1             0
Other Reason             0             1             0
Extension ongoing             9             69             0
[1]
Not all participants from main trial entered extension or remained in the same arm.
[2]
Participants in Part B were not counted for part A
Period Title: Part B
Started [1] 0 [2] 0 [2] 19 [3]
Part B Ongoing 0 0 1
Completed 0 0 16
Not Completed 0 0 3
Reason Not Completed
Withdrawal by Subject             0             0             1
Other reason             0             0             1
Part B ongoing             0             0             1
[1]
Treated in Part B
[2]
Time in Part A for 8 participants coming from Part A was not counted in part B.
[3]
11 participants were enrolled in Part B only, 8 participants switched from Part A to Part B.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Dropped, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Treatment in Major Surgery, Part B Only Total
Hide Arm/Group Description Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]). 4 participants dropped out during week 0-10 All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg. All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’). All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion. All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days. Participants treated in Part B only were included. Participants treated in Part A and continued in Part B were excluded. Participants who underwent major surgery received study drug during their hospital stay and up until hospital discharge or 3 weeks post-surgery, whichever came first. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg) expected to maintain acceptable therapeutic level of FVIII activity. Total of all reporting groups
Overall Number of Baseline Participants 20 4 13 11 43 43 11 145
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 4 participants 13 participants 11 participants 43 participants 43 participants 11 participants 145 participants
44.8  (13.5) 27.3  (14.2) 31.4  (11.6) 33.1  (11.0) 33.7  (13.0) 37.0  (13.5) 37.9  (13.7) 36.1  (13.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 4 participants 13 participants 11 participants 43 participants 43 participants 11 participants 145 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
20
 100.0%
4
 100.0%
13
 100.0%
11
 100.0%
43
 100.0%
43
 100.0%
11
 100.0%
145
 100.0%
1.Primary Outcome
Title Annualized Number of Total Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) – Part A, Main Trial
Hide Description Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds. A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the annualized bleeding rate (ABR).
Time Frame On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population part A week 10-36, 4 participants dropped out during week 0-10.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 20 13 11 43 43 110
Median (Inter-Quartile Range)
Unit of Measure: bleeds
23.42
(17.84 to 37.25)
4.11
(2.01 to 10.56)
1.93
(0.00 to 5.24)
1.93
(0.00 to 4.23)
3.85
(0.00 to 6.47)
2.09
(0.00 to 6.05)
2.Secondary Outcome
Title Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) – Part A
Hide Description A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the ABR.
Time Frame On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population part A week 10-36, 4 participants dropped out during week 0-10.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 20 13 11 43 43 110
Median (Inter-Quartile Range)
Unit of Measure: bleeds
Joint Bleeds
16.34
(11.61 to 30.30)
4.01
(1.98 to 8.03)
1.93
(0.00 to 5.24)
1.86
(0.00 to 3.99)
1.92
(0.00 to 6.26)
1.93
(0.00 to 5.24)
Trauma Bleeds
9.09
(3.08 to 15.53)
1.98
(0.00 to 5.80)
0.00
(0.00 to 1.93)
0.00
(0.00 to 2.09)
0.00
(0.00 to 0.00)
0.00
(0.00 to 1.98)
Spontaneous Bleeds
14.29
(7.26 to 22.71)
3.87
(0.00 to 4.11)
0.00
(0.00 to 1.93)
0.00
(0.00 to 3.99)
1.93
(0.00 to 6.33)
0.00
(0.00 to 4.17)
3.Secondary Outcome
Title Annualized Number of Total Bleeds in On-demand Treatment Arm and in Each Prophylaxis Arm, Part A, Extension
Hide Description Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.
Time Frame at least 100 total exposure days acquired, Median (range) time in extension: 464 days (45-700)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT extension population. Participants in each regimen stayed on this regimen without switch. Participants who switched regimen were analyzed in the variable frequency arm.
Arm/Group Title BAY94-9027 On-demand Treatment, Extension BAY94-9027 Prophylaxis Treatment, 2x/Week, Extension BAY94-9027 Prophylaxis Treatment, Every 5 Days, Extension BAY94-9027 Prophylaxis Treatment, Every 7 Days, Extension BAY94-9027 Prophylaxis Treatment, Variable, Extension
Hide Arm/Group Description:
On-demand participants entering the Part A extension either continued their on-demand treatment or switched to one of the prophylaxis regimens.
Prophylaxis participants entering the Part A extension were either to continue their prophylaxis regimen as it was at the conclusion of the main trial, or had the option of switching to one of the other prophylaxis regimens.
Prophylaxis participants entering the Part A extension were either to continue their prophylaxis regimen as it was at the conclusion of the main trial, or had the option of switching to one of the other prophylaxis regimens.
Prophylaxis participants entering the Part A extension were either to continue their prophylaxis regimen as it was at the conclusion of the main trial, or had the option of switching to one of the other prophylaxis regimens.
Participants changed their treatment regimens at least once after 1st week in extension.
Overall Number of Participants Analyzed 14 24 37 29 17
Median (Inter-Quartile Range)
Unit of Measure: bleeds
32.96
(22.55 to 35.64)
2.21
(0.39 to 4.32)
1.17
(0.00 to 5.59)
0.54
(0.00 to 1.04)
3.94
(1.19 to 6.36)
4.Secondary Outcome
Title Number of Participants Developed Human Coagulation Factor VIII (FVIII) Inhibitor – Part A
Hide Description FVIII inhibitor testing was done according to the Nijmegen modified Bethesda assay. A positive inhibitor test was defined with a threshold of ≥0.6 Bethesda unit (BU) at the central laboratory.
Time Frame Weeks 0 to 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
Part A safety population (N=134) included all participants who received at least 1 dose of study drug during Part A of the study.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 20 114
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Number of Bleeds Requiring 1, 2 or >= 3 Infusions to Control the Bleed – Part A
Hide Description Number of bleeds requiring 1, 2 or >= 3 infusions to control the bleeding
Time Frame Weeks 0 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
Part A ITT population, analysis population includes participants who presented >=1 bleeding event.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 20 75
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeds
386 316
Measure Type: Number
Unit of Measure: bleeds
1 infusion 307 262
2 infusions 45 22
Greater than or equal to (>=) 3 infusions 34 32
6.Secondary Outcome
Title Number of Bleeds According to Locations – Part A
Hide Description Bleed locations were categorised as joint, muscle, skin/mucosa, internal, others and missing.
Time Frame Weeks 0 -36
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population includes participants who presented >=1 bleeding event.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 20 75
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeds
386 316
Measure Type: Number
Unit of Measure: bleeds
Missing 0 0
Joint 303 235
Muscle 54 59
Skin/Mucosa 12 12
Internal 7 7
Other 26 16
7.Secondary Outcome
Title Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A
Hide Description [Not Specified]
Time Frame Weeks 0 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population includes participants who presented >=1 bleeding event.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 20 75
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeds
386 316
Measure Type: Number
Unit of Measure: bleeds
<1 day 4 21
>=1 to <2 days 19 62
>=2 to <3 days 30 82
>=3 to <4 days 30 69
>=4 to <5 days 38 32
>=5 to <6 days 42 36
>=6 to <7 days 31 11
>=7 days 192 3
8.Secondary Outcome
Title Number of Bleeds According to Participant's Assessment of Response to Treatment – Part A
Hide Description Response to treatment was assessed by participant as excellent, good, moderate, poor or missing during Part A of the study.
Time Frame Weeks 0 to 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population includes participants who presented >=1 bleeding event.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 20 75
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeds
386 316
Measure Type: Number
Unit of Measure: bleeds
Excellent or Good 252 256
Excellent 81 107
Good 171 149
Moderate 115 47
Poor 16 7
Missing 3 6
9.Secondary Outcome
Title Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose Per Kilogram Per Year – Part A
Hide Description For prophylaxis patients, the dose is related to all infusions.
Time Frame On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population part A week 10-36, 4 participants dropped out during week 0-10.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 20 13 11 43 43 110
Median (Full Range)
Unit of Measure: IU/kg/year
1518.5
(390 to 3655)
4421.4
(3759 to 5978)
3314.4
(2651 to 4062)
3482.9
(2936 to 6774)
3338.7
(2764 to 5789)
3421.0
(2651 to 6774)
10.Secondary Outcome
Title Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram Per Infusion - Part A
Hide Description For prophylaxis patients, the dose per infusion related to prophylaxis infusion.
Time Frame On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population part A week 10-36, 4 participants dropped out during week 0-10.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 20 13 11 43 43 110
Median (Full Range)
Unit of Measure: IU/kg/infusion
32.8
(23 to 58)
39.2
(33 to 42)
30.6
(29 to 41)
45.3
(39 to 58)
59.0
(51 to 64)
46.9
(29 to 64)
11.Secondary Outcome
Title Number of Participants Requiring an Increase in Dose Frequency, or Dose Increase, During Weeks 10 to 36 - Part A
Hide Description [Not Specified]
Time Frame Weeks 10 to 36 during Part A
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ITT population part A week 10-36, 4 participants dropped out during week 0-10.
Arm/Group Title BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 13 11 43 43 110
Measure Type: Count of Participants
Unit of Measure: Participants
Dose frequency increased
0
   0.0%
0
   0.0%
0
   0.0%
11
  25.6%
11
  10.0%
Dose increased
2
  15.4%
0
   0.0%
7
  16.3%
0
   0.0%
9
   8.2%
12.Secondary Outcome
Title Number of Surgeries According to Physician's Assessment of Adequacy of Hemostasis in Major Surgery – Part B
Hide Description Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Adequacy of hemostasis was assessed as excellent, good, moderate or poor, by the surgeon or interventionalist during Part B of the study.
Time Frame Day of surgery
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17 participants were included in the Part B ITT population.
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 17
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
20
Measure Type: Number
Unit of Measure: surgeries
Good 13
Excellent 7
Moderate 0
Poor 0
13.Secondary Outcome
Title Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram Per Infusion for Major Surgery – Part B
Hide Description Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Total dose per kilogram per Infusion was expressed in international units per kilogram per infusion (IU/kg/infusion).
Time Frame Up to 3 weeks post-surgery during Part B
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Hide Analysis Population Description
Part B ITT population
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 17
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
20
Median (Full Range)
Unit of Measure: IU/kg/infusion
33.7
(22 to 51)
14.Secondary Outcome
Title Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery – Part B
Hide Description Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.rFVIII usage expressed as number of infusions and IU/kg per year, as well as IU/kg per event (surgery) was assessed by investigator.
Time Frame Up to 3 weeks post-surgery during Part B
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Hide Analysis Population Description
Part B ITT population
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 17
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
20
Median (Full Range)
Unit of Measure: infusions
8.0
(3 to 39)
15.Secondary Outcome
Title Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay – Part A
Hide Description Cmax: Maximum observed drug concentration following an infusion of 60 IU/kg
Time Frame Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
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Hide Analysis Population Description
Pharmacokinetic Analysis Set (PKS) with participants evaluable for this outcome, PKS included all participants with a valid profile of BAY94-9027 during Part A of the study.
Arm/Group Title BAY94-9027 Treatment – Part A, Week 0 BAY94-9027 Treatment – Part A, Week 36
Hide Arm/Group Description:
Part A, Week 0 included all PKS participants treated with a single (first) dose of BAY94-9027 as an IV infusion at Week 0.
Part A, Week 36 group included all PKS participants treated with multiple doses (last dose paired) of BAY94-9027 as an IV infusion at Week 36. Paired data were defined as the single dose data for the sub-set of participants who also had multiple dose PK data.
Overall Number of Participants Analyzed 22 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: IU/dL
162.8
(14.74%)
177.1
(20.98%)
16.Secondary Outcome
Title Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay – Part A
Hide Description AUC: The total area under the plasma concentration versus time curve following an infusion of 60 IU/kg .
Time Frame Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PKS with participants evaluable for this outcome
Arm/Group Title BAY94-9027 Treatment – Part A, Week 0 BAY94-9027 Treatment – Part A, Week 36
Hide Arm/Group Description:
Part A, Week 0 included all PKS participants treated with a single (first) dose of BAY94-9027 as an IV infusion at Week 0.
Part A, Week 36 group included all PKS participants treated with multiple doses (last dose paired) of BAY94-9027 as an IV infusion at Week 36. Paired data were defined as the single dose data for the sub-set of participants who also had multiple dose PK data.
Overall Number of Participants Analyzed 22 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*IU/dL
3707.5
(33.77%)
4130.8
(28.8%)
17.Secondary Outcome
Title Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay – Part A
Hide Description t1/2: Terminal half-life is the time the plasma concentration during terminal phase is halved following an infusion of 60 IU/kg .
Time Frame Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PKS with participants evaluable for this outcome
Arm/Group Title BAY94-9027 Treatment – Part A, Week 0 BAY94-9027 Treatment – Part A, Week 36
Hide Arm/Group Description:
Part A, Week 0 included all PKS participants treated with a single (first) dose of BAY94-9027 as an IV infusion at Week 0.
Part A, Week 36 group included all PKS participants treated with multiple doses (last dose paired) of BAY94-9027 as an IV infusion at Week 36. Paired data were defined as the single dose data for the sub-set of participants who also had multiple dose PK data.
Overall Number of Participants Analyzed 22 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
17.1
(27.05%)
19.6
(38.48%)
18.Secondary Outcome
Title Overall Human Coagulation Factor VIII (FVIII) Recovery Value by Chromogenic Assay – Part A
Hide Description Recovery was calculated by the following formula: Recovery = (post-infusion FVIII activity – pre-infusion FVIII activity ) * weight / dose (in IU). Recovery is the increase of FVIII activity after the injection normalized by dose: IU/dl per IU/kg = kg/dL
Time Frame Weeks 0 to 36 during Part A
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Hide Analysis Population Description
Part A ITT population
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 20 112
Mean (Standard Deviation)
Unit of Measure: Kilogram per deciliter
2.67  (0.54) 2.68  (0.55)
19.Secondary Outcome
Title Change From Baseline in Quality of Life by Hemophilia Specific Quality of Life Instrument or Questionnaire for Adults (Haemo-QoL-A) Overall Score at Week 36 – Part A
Hide Description Quality of life (QoL) was measured by the Haemo-QoL-A overall score, which ranged from 0 (the worst condition) to 100 (the best condition).
Time Frame Week 0 (baseline) and Week 36 during Part A
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Hide Analysis Population Description
Part A ITT population with participants evaluable for this outcome
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 19 97
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.14  (9.70) 2.59  (7.98)
20.Other Pre-specified Outcome
Title Change From Baseline in Overall Pain Severity and Interference Due to Pain at Week 36 – Part A
Hide Description Brief Pain Inventory (BPI) – Short Form (BPI-SF) was a 15-item, self-administered, validated tool developed to assess pain used in the study for patient reported outcomes. Scores ranged from 0 to 10 and a higher score indicates a higher level of pain/interference.
Time Frame Week 0 (baseline) and Week 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population includes participants evaluable in each category for this outcome.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week ‘failed’). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).
Overall Number of Participants Analyzed 20 112
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Pain severity subscale Number Analyzed 15 participants 78 participants
-0.8  (1.8) 0.1  (1.39)
Interference subscale Number Analyzed 15 participants 77 participants
-0.99  (2.54) -0.06  (1.39)
21.Other Pre-specified Outcome
Title Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 – Part A
Hide Description The WPAI is a validated instrument to assess the effect of hemophilia on ability to work, attend classes, and perform regular daily activities in participants aged 12 and above. The WPAI also contained classroom impairment questions (CIQ). The questionnaire was self-administered and comprised of nine questions that elicited information on work, classroom, and daily activity impairment during the previous seven days. WPAI outcomes that are overall work and activity impairment, transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Time Frame Week 0 (baseline) and Week 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population includes participants evaluable in each category for this outcome.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 20 112
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Activity impairment Number Analyzed 20 participants 108 participants
4.74  (24.12) -7.13  (20.00)
Overall work impairment Number Analyzed 12 participants 62 participants
4.44  (21.94) -1.22  (21.94)
22.Other Pre-specified Outcome
Title Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions– Part A
Hide Description For prophylaxis patients, the dose is related to all infusions.
Time Frame On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
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Hide Analysis Population Description
ITT population part A week 10-36, 4 participants dropped out during week 0-10.
Arm/Group Title BAY94-9027 On-demand Treatment, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 20 13 11 43 43 110
Median (Full Range)
Unit of Measure: infusions
29
(9 to 76)
56.0
(52 to 71)
55.0
(47 to 59)
38.0
(3 to 58)
27.0
(5 to 63)
37.5
(3 to 71)
23.Other Pre-specified Outcome
Title Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram With Prophylaxis Treatment – Part A
Hide Description For prophylaxis patients, the dose per kilogram is related to prophylaxis infusions.
Time Frame Weeks 10 - 36 during Part A
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population part A week 10-36, 4 participants dropped out during week 0-10.
Arm/Group Title BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial BAY94-9027 Prophylaxis Treatment Total, Main Trial
Hide Arm/Group Description:
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week ‘failed’) at a dose of 30 to 40 IU/kg.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week ‘forced’).
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Number of Participants Analyzed 13 11 43 43 110
Median (Full Range)
Unit of Measure: IU/kg
1986.9
(1733 to 2236)
1669.1
(1430 to 1947)
1704.3
(139 to 2049)
1530.2
(122 to 1788)
1644.9
(122 to 2236)
24.Other Pre-specified Outcome
Title Number of Minor Surgeries According to Physician's Assessment of Adequacy of Hemostasis – Part A
Hide Description Minor surgery was defined as any surgical procedure that did not meet the definition of major, and included simple dental extractions, incision and drainage of abscesses, or simple excisions.
Time Frame Weeks 0 to 36 during Part A
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Hide Analysis Population Description
Part A ITT population
Arm/Group Title BAY94-9027 Treatment - Part A
Hide Arm/Group Description:
This group included both on-demand and prophylaxis arms in Part A.
Overall Number of Participants Analyzed 10
Overall Number of Units Analyzed
Type of Units Analyzed: Minor surgeries
17
Measure Type: Number
Unit of Measure: minor surgeries
Excellent 9
Good 6
Missing 2
25.Other Pre-specified Outcome
Title Number of Surgeries According to Physician’s Assessment of Response to Hemostasis, Post-surgery - Part B Main Trial
Hide Description Response to treatment during surgery was assessed by investigator/surgeon as excellent, good, moderate, poor or missing during Part B of the study.
Time Frame Up to 3 weeks post-surgery during Part B
Hide Outcome Measure Data
Hide Analysis Population Description
Part B ITT population
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 14
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
17
Measure Type: Number
Unit of Measure: surgeries
Excellent 8
Good 5
Moderate 3
Missing 1
26.Other Pre-specified Outcome
Title Number of Participants With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments – Part B
Hide Description Hematocrit is defined as the volume percentage (%) of red blood cells in blood.
Time Frame Up to 3 weeks post-surgery during Part B
Hide Outcome Measure Data
Hide Analysis Population Description
Part B Safety population (N=17) included all participants who received at least 1 dose of study drug during Part B of the study.
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 17
Measure Type: Count of Participants
Unit of Measure: Participants
Hematocrit
6
  35.3%
Hemoglobin
2
  11.8%
27.Other Pre-specified Outcome
Title Maximum Blood Loss During Major Surgery – Part B
Hide Description Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.
Time Frame day of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Part B ITT population with participants treated for major surgery
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 17
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
20
Measure Type: Number
Unit of Measure: milliliter
1000
28.Other Pre-specified Outcome
Title Number of Participants Who Took Anti-fibrinolytic Medications During Major Surgery – Part B
Hide Description Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.
Time Frame Up to 3 weeks post-surgery during Part B
Hide Outcome Measure Data
Hide Analysis Population Description
Part B ITT population with participants treated for major surgery
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 17
Measure Type: Count of Participants
Unit of Measure: Participants
8
  47.1%
29.Other Pre-specified Outcome
Title Volume of Blood Transfused in Major Surgery - Part B
Hide Description Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.
Time Frame Up to 3 weeks post-surgery during Part B
Hide Outcome Measure Data
Hide Analysis Population Description
Part B ITT population who had blood transfusions during major surgery
Arm/Group Title BAY949027 Treatment in Major Surgery, Part B
Hide Arm/Group Description:
Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Overall Number of Participants Analyzed 4
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
5
Median (Full Range)
Unit of Measure: milliliter
865
(600 to 1380)
Time Frame Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately two years.
Adverse Event Reporting Description The Adverse Events present the data for the on-going extension of the main trial (Part A and B) as of 09 Jan 2015.
 
Arm/Group Title BAY94-9027 On-demand Treatment, Part A BAY94-9027 Prophylaxis Treatment, Part A BAY94-9027 Treatment in Major Surgery, Part B
Hide Arm/Group Description Participants received on-demand treatment with BAY94-9027 as an intravenous (IV) infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]). Participants entering extension either continued their on-demand treatment or switched to one of the prophylaxis regimens. All participants started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group). Participants entering extension either continued their prophylaxis regimen or switched to one of the other prophylaxis regimens. Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post-surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
All-Cause Mortality
BAY94-9027 On-demand Treatment, Part A BAY94-9027 Prophylaxis Treatment, Part A BAY94-9027 Treatment in Major Surgery, Part B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)      0/114 (0.00%)      0/19 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
BAY94-9027 On-demand Treatment, Part A BAY94-9027 Prophylaxis Treatment, Part A BAY94-9027 Treatment in Major Surgery, Part B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/20 (20.00%)      28/114 (24.56%)      2/19 (10.53%)    
Eye disorders       
Macular fibrosis * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Gastrointestinal disorders       
Anal fistula * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Gastrointestinal haemorrhage * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Mouth haemorrhage * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Pancreatitis acute * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Tooth impacted * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Retroperitoneal haematoma * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Hepatobiliary disorders       
Bile duct stone * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Immune system disorders       
Drug hypersensitivity * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Infections and infestations       
Gastroenteritis * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Pneumonia * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Anal abscess * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Arthritis bacterial * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Device related infection * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Injury, poisoning and procedural complications       
Alcohol poisoning * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Head injury * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Humerus fracture * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Injury * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Overdose * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Tendon rupture * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Investigations       
Colonoscopy * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Anti factor VIII antibody positive * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 2/19 (10.53%)  2
Liver function test increased * 1  0/20 (0.00%)  0 1/114 (0.88%)  2 0/19 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthropathy * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Back pain * 1  0/20 (0.00%)  0 1/114 (0.88%)  2 0/19 (0.00%)  0
Chondrocalcinosis pyrophosphate * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Haemarthrosis * 1  0/20 (0.00%)  0 2/114 (1.75%)  2 0/19 (0.00%)  0
Rotator cuff syndrome * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Synovitis * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Haemophilic arthropathy * 1  0/20 (0.00%)  0 3/114 (2.63%)  3 0/19 (0.00%)  0
Nervous system disorders       
Epilepsy * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Product Issues       
Device malfunction * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 0/19 (0.00%)  0
Surgical and medical procedures       
Knee arthroplasty * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Vascular disorders       
Haematoma * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 1/19 (5.26%)  1
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BAY94-9027 On-demand Treatment, Part A BAY94-9027 Prophylaxis Treatment, Part A BAY94-9027 Treatment in Major Surgery, Part B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/20 (85.00%)      83/114 (72.81%)      14/19 (73.68%)    
Blood and lymphatic system disorders       
Anaemia * 1  1/20 (5.00%)  1 1/114 (0.88%)  2 0/19 (0.00%)  0
Splenomegaly * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Cardiac disorders       
Tachycardia * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Eye disorders       
Cataract * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain lower * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Diarrhoea * 1  1/20 (5.00%)  1 6/114 (5.26%)  8 0/19 (0.00%)  0
Melaena * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Nausea * 1  1/20 (5.00%)  1 6/114 (5.26%)  8 0/19 (0.00%)  0
Dental caries * 1  1/20 (5.00%)  1 5/114 (4.39%)  6 0/19 (0.00%)  0
Dry mouth * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Food poisoning * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Gastric ulcer * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Haemorrhoids * 1  1/20 (5.00%)  2 3/114 (2.63%)  4 0/19 (0.00%)  0
Inguinal hernia * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Toothache * 1  2/20 (10.00%)  2 3/114 (2.63%)  3 0/19 (0.00%)  0
General disorders       
Hyperthermia * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  2
Pyrexia * 1  1/20 (5.00%)  1 7/114 (6.14%)  8 3/19 (15.79%)  3
Chills * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Fatigue * 1  1/20 (5.00%)  1 3/114 (2.63%)  4 0/19 (0.00%)  0
Injection site rash * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Peripheral swelling * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Hepatobiliary disorders       
Cholelithiasis * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Hepatic steatosis * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Immune system disorders       
Drug hypersensitivity * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Infections and infestations       
Influenza * 1  0/20 (0.00%)  0 8/114 (7.02%)  17 0/19 (0.00%)  0
Lymphangitis * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Nasopharyngitis * 1  2/20 (10.00%)  4 31/114 (27.19%)  51 1/19 (5.26%)  1
Pharyngitis * 1  0/20 (0.00%)  0 7/114 (6.14%)  7 0/19 (0.00%)  0
Upper respiratory tract infection * 1  2/20 (10.00%)  2 7/114 (6.14%)  8 0/19 (0.00%)  0
Acute sinusitis * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Cellulitis * 1  1/20 (5.00%)  2 0/114 (0.00%)  0 0/19 (0.00%)  0
Gastroenteritis * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Herpes zoster * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Localised infection * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Otitis externa * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Otitis media * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Periodontitis * 1  1/20 (5.00%)  1 2/114 (1.75%)  2 0/19 (0.00%)  0
Oral infection * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Injury, poisoning and procedural complications       
Anaemia postoperative * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Procedural hypotension * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Post procedural oedema * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  2
Procedural pain * 1  0/20 (0.00%)  0 4/114 (3.51%)  5 5/19 (26.32%)  6
Procedural nausea * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Procedural haemorrhage * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 3/19 (15.79%)  3
Arthropod bite * 1  1/20 (5.00%)  1 2/114 (1.75%)  2 0/19 (0.00%)  0
Fall * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Ligament sprain * 1  1/20 (5.00%)  1 5/114 (4.39%)  7 0/19 (0.00%)  0
Skin abrasion * 1  1/20 (5.00%)  1 3/114 (2.63%)  3 0/19 (0.00%)  0
Investigations       
Haemoglobin decreased * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 3/19 (15.79%)  3
Alanine aminotransferase increased * 1  1/20 (5.00%)  2 2/114 (1.75%)  2 0/19 (0.00%)  0
Blood magnesium decreased * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Blood pressure increased * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Metabolism and nutrition disorders       
Hyperglycaemia * 1  1/20 (5.00%)  2 1/114 (0.88%)  1 0/19 (0.00%)  0
Hypertriglyceridaemia * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Hypokalaemia * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  1/20 (5.00%)  1 19/114 (16.67%)  24 1/19 (5.26%)  1
Arthritis * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Back pain * 1  0/20 (0.00%)  0 15/114 (13.16%)  21 0/19 (0.00%)  0
Haemarthrosis * 1  1/20 (5.00%)  1 5/114 (4.39%)  5 1/19 (5.26%)  1
Pain in extremity * 1  1/20 (5.00%)  1 7/114 (6.14%)  11 0/19 (0.00%)  0
Joint swelling * 1  1/20 (5.00%)  1 2/114 (1.75%)  2 0/19 (0.00%)  0
Extremity contracture * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Musculoskeletal discomfort * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Nervous system disorders       
Headache * 1  1/20 (5.00%)  1 19/114 (16.67%)  35 0/19 (0.00%)  0
Product Issues       
Device loosening * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Psychiatric disorders       
Insomnia * 1  0/20 (0.00%)  0 4/114 (3.51%)  4 1/19 (5.26%)  1
Anxiety * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Renal and urinary disorders       
Haematuria * 1  1/20 (5.00%)  2 1/114 (0.88%)  1 0/19 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough * 1  2/20 (10.00%)  3 8/114 (7.02%)  11 0/19 (0.00%)  0
Epistaxis * 1  0/20 (0.00%)  0 9/114 (7.89%)  12 0/19 (0.00%)  0
Oropharyngeal pain * 1  0/20 (0.00%)  0 3/114 (2.63%)  3 1/19 (5.26%)  1
Dyspnoea * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
Rhinitis allergic * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dermatitis * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 1/19 (5.26%)  1
Haemorrhage subcutaneous * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 1/19 (5.26%)  1
Ingrowing nail * 1  0/20 (0.00%)  0 0/114 (0.00%)  0 1/19 (5.26%)  1
Dermatitis allergic * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Diabetic foot * 1  1/20 (5.00%)  1 0/114 (0.00%)  0 0/19 (0.00%)  0
Vascular disorders       
Haematoma * 1  0/20 (0.00%)  0 1/114 (0.88%)  1 2/19 (10.53%)  2
Hypertension * 1  1/20 (5.00%)  1 1/114 (0.88%)  1 0/19 (0.00%)  0
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Some registered "Secondary outcome measure" were re-classified as "Other Pre-specified" in line with protocol.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer AG
Phone: (+) 1-888-8422937
EMail: clinical-trials-contact@bayer.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01580293     History of Changes
Other Study ID Numbers: 13024
2011-005210-11 ( EudraCT Number )
First Submitted: March 28, 2012
First Posted: April 19, 2012
Results First Submitted: September 26, 2018
Results First Posted: December 6, 2018
Last Update Posted: September 18, 2019