Trial Outcomes & Findings for Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds (NCT NCT00486278)

NCT ID: NCT00486278

Last Updated: 2017-03-07

Results Overview

Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 51 participants
• Primary outcome timeframe: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.
• Results posted on: 2017-03-07

Participant Flow

A total of 40 sites were initiated globally in 18 countries, including Argentina, Brazil, Canada, Croatia, France, Hungary, Israel, Italy, Japan, Malaysia, Poland, South Africa, Spain, Turkey, Taiwan, Thailand, the United Kingdom and the United States

A subject could be included in more than one dose escalation cohort with up to one bleeding per cohort, randomised by 4:1 to receive either vatreptacog alfa or rFVIIa 90 (mcg/kg) in a blinded manner.

Participant milestones

Measure	All Subjects A total of 51 subjects with 96 qualifying bleeds were treated in the study. A subject could contribute with up to one qualifying bleeding episode per study arm.
Overall Study STARTED	51
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Measure	All Subjects A total of 51 subjects with 96 qualifying bleeds were treated in the study. A subject could contribute with up to one qualifying bleeding episode per study arm.
Overall Study Adverse Event	5
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	2

Baseline Characteristics

Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds

Baseline characteristics by cohort

Measure	All Subjects n=51 Participants A total of 51 subjects with 96 qualifying bleeds were treated in the study. A subject could contribute with up to one qualifying bleeding episode per study arm.
Age, Continuous	28 years STANDARD_DEVIATION 12.4 • n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	51 Participants n=93 Participants

PRIMARY outcome

Timeframe: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Number of Adverse Events (AEs) All AEs	10 events	8 events	5 events	5 events	0 events	11 events
Number of Adverse Events (AEs) Serious AEs	3 events	5 events	2 events	2 events	0 events	3 events

SECONDARY outcome

Timeframe: 0-24 hours after trial product administration

Population: All randomised patients in top three dosing tiers 3, 4 and 5 who had pharmacokinetic assessments and completed the trial without violation of the protocol in a manner that was judged to affect the pharmacokinetic endpoints were included in the pharmacokinetic analysis set.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Activated Recombinant Human Factor VII Analogue Activity in the Blood Pre-dose	—	—	0.1 IU/mL Standard Deviation 0.1	0.1 IU/mL Standard Deviation 0	0 IU/mL Standard Deviation 0	0.1 IU/mL Standard Deviation 0
Activated Recombinant Human Factor VII Analogue Activity in the Blood 1 hours post-dose	—	—	5.3 IU/mL Standard Deviation 1.3	12.8 IU/mL Standard Deviation 5.3	19.7 IU/mL Standard Deviation 7.2	28.0 IU/mL Standard Deviation 12.6
Activated Recombinant Human Factor VII Analogue Activity in the Blood 12 hours post-dose	—	—	0.4 IU/mL Standard Deviation 0.4	2.3 IU/mL Standard Deviation 4.5	0.3 IU/mL Standard Deviation 0.3	14.1 IU/mL Standard Deviation 27.3
Activated Recombinant Human Factor VII Analogue Activity in the Blood 24 hours post-dose	—	—	0 IU/mL Standard Deviation 0	0 IU/mL Standard Deviation 0	0 IU/mL Standard Deviation 0	0.1 IU/mL Standard Deviation 0

SECONDARY outcome

Timeframe: pre-dose - 12 hours after trial product administration

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

The test measures the clotting time of plasma following the activation of tissue factor (TF also called thromboplastin) and calcium to hypocalcemic plasma. PT was provided in percent based on the measured PT in seconds and related/converted with the relevant standard curve. The percent value was derived based on the hyperbolic relation between PT (sec) and % PT activity.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Prothrombin Time (PT) Pre-dose	80.1 percentage (%) Standard Deviation 12.6	77.6 percentage (%) Standard Deviation 19.1	79.1 percentage (%) Standard Deviation 14.9	85.9 percentage (%) Standard Deviation 15.5	85.5 percentage (%) Standard Deviation 8.8	88.3 percentage (%) Standard Deviation 25.6
Prothrombin Time (PT) 1 hours post-dose	84.3 percentage (%) Standard Deviation 16.3	99.6 percentage (%) Standard Deviation 17.9	112.1 percentage (%) Standard Deviation 14.6	123.4 percentage (%) Standard Deviation 14.7	128.5 percentage (%) Standard Deviation 7.6	139.0 percentage (%) Standard Deviation 0
Prothrombin Time (PT) 12 hours post-dose	82.1 percentage (%) Standard Deviation 16.2	73.2 percentage (%) Standard Deviation 19.2	86.9 percentage (%) Standard Deviation 14.1	94.5 percentage (%) Standard Deviation 17.5	92.3 percentage (%) Standard Deviation 16.8	112.1 percentage (%) Standard Deviation 29.1

SECONDARY outcome

Timeframe: pre-dose - 12 hours after trial product administration

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

Thrombin and F1+2 are formed in equimolar quantities by the enzymatic cleavage of prothrombin (FII), and F1+2 thus indicate that thrombin has been generated.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
F1 + 2 (Prothrombin Fragments 1+2) Pre-dose	289.8 pmol/L Standard Deviation 310.9	131.8 pmol/L Standard Deviation 48.7	139.1 pmol/L Standard Deviation 50.4	121.2 pmol/L Standard Deviation 34.5	125.4 pmol/L Standard Deviation 45.9	169.3 pmol/L Standard Deviation 56.9
F1 + 2 (Prothrombin Fragments 1+2) 1 hour post-dose	443.7 pmol/L Standard Deviation 414.7	241.7 pmol/L Standard Deviation 162.0	401.6 pmol/L Standard Deviation 292.6	365.9 pmol/L Standard Deviation 145.4	385.7 pmol/L Standard Deviation 88.8	309.7 pmol/L Standard Deviation 284.5
F1 + 2 (Prothrombin Fragments 1+2) 12 hour post-dose	325.9 pmol/L Standard Deviation 299.4	198.9 pmol/L Standard Deviation 250.9	158.6 pmol/L Standard Deviation 54.5	199.8 pmol/L Standard Deviation 91.5	136.9 pmol/L Standard Deviation 43.8	268.2 pmol/L Standard Deviation 158.0

SECONDARY outcome

Timeframe: pre-dose - 12 hours after trial product administration

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

The aPTT time measured in clinical samples reflects both the effect of the drugs (generation of thrombin and FXa) and the presence of rFVIIa /rFVIIa analogue in the plasma samples causing a dose dependent shortening of the clotting time.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Activated Partial Thromboplastin Time (aPTT) Pre-dose	120.6 Sec Standard Deviation 22.6	126.0 Sec Standard Deviation 26.4	122.8 Sec Standard Deviation 15.9	119.2 Sec Standard Deviation 31.3	117.4 Sec Standard Deviation 17.9	113.8 Sec Standard Deviation 17.4
Activated Partial Thromboplastin Time (aPTT) 1 hours post-dose	102.1 Sec Standard Deviation 19.4	79.7 Sec Standard Deviation 13.9	68.7 Sec Standard Deviation 15.7	52.8 Sec Standard Deviation 14.1	48.6 Sec Standard Deviation 24.0	70.0 Sec Standard Deviation 9.8
Activated Partial Thromboplastin Time (aPTT) 12 hours post-dose	111.7 Sec Standard Deviation 22.4	107.9 Sec Standard Deviation 27.7	107.9 Sec Standard Deviation 14.8	104.4 Sec Standard Deviation 31.2	99.3 Sec Standard Deviation 19.6	98.6 Sec Standard Deviation 20.8

SECONDARY outcome

Timeframe: Within 9 hours after first trial product administration or need of additional haemostatic medication within 9 hours after first trial administration additional haemostatic agents required to control bleed (treatment failure)

Population: All randomised patients for whom at least one of the efficacy variables is assessed were to be included in the full analysis set (FAS). For the outcome measure 1 subject did not contribute to the data.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=15 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Cessation of Bleeding: Number of Doses Needed to Control Bleeding 1 dose	3 bleeding episodes	3 bleeding episodes	2 bleeding episodes	5 bleeding episodes	4 bleeding episodes	6 bleeding episodes
Cessation of Bleeding: Number of Doses Needed to Control Bleeding 2 doses	5 bleeding episodes	9 bleeding episodes	7 bleeding episodes	6 bleeding episodes	4 bleeding episodes	4 bleeding episodes
Cessation of Bleeding: Number of Doses Needed to Control Bleeding 3 doses	4 bleeding episodes	4 bleeding episodes	7 bleeding episodes	4 bleeding episodes	2 bleeding episodes	7 bleeding episodes
Cessation of Bleeding: Number of Doses Needed to Control Bleeding treatment failure	3 bleeding episodes	3 bleeding episodes	0 bleeding episodes	1 bleeding episodes	0 bleeding episodes	2 bleeding episodes

SECONDARY outcome

Timeframe: within 24 hours after successful control of bleeding episode with trial product

Population: All randomised patients for whom at least one of the efficacy variables is assessed were to be included in the full analysis set (FAS). For the outcome measure 9 subjects did not contribute to the data.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=12 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=16 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=15 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Number of Subjects With Need for Additional Haemostatic Agents	4 participants	1 participants	1 participants	1 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: 0-24 hours after trial product administration

Population: All randomised patients in top 3 dosing tiers 3, 4 and 5 who had pharmacokinetic assessments and completed the trial without violating the protocol in a manner that was judged to affect the pharmacokinetic endpoints were included in the pharmacokinetic analysis set. Some subjects did not contribute for pharmacokinetic analysis.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=11 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=11 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=7 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=7 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Pharmacokinetic Parameters Based on FVIIa Activity: AUC 0-t (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to the Time (t) )	—	—	34.24 (IU*h)/mL Geometric Coefficient of Variation 27.00	66.85 (IU*h)/mL Geometric Coefficient of Variation 50.51	136.19 (IU*h)/mL Geometric Coefficient of Variation 18.56	74.35 (IU*h)/mL Geometric Coefficient of Variation 45.30

SECONDARY outcome

Timeframe: 0-24 hours after trial product administration

Population: All randomised patients in top 3 dosing tiers 3, 4 and 5 who had pharmacokinetic assessments and completed the trial without violating the protocol in a manner that was judged to affect the pharmacokinetic endpoints were included in the pharmacokinetic analysis set. Some subjects did not contribute for pharmacokinetic analysis.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=11 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=11 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=7 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=7 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Pharmacokinetic Parameters Based on FVIIa Activity: AUC(0-inf) (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to Infinity)	—	—	35.76 (IU*h)/mL Geometric Coefficient of Variation 26.34	71.23 (IU*h)/mL Geometric Coefficient of Variation 55.42	139.63 (IU*h)/mL Geometric Coefficient of Variation 18.35	101.38 (IU*h)/mL Geometric Coefficient of Variation 40.77

SECONDARY outcome

Timeframe: 0-24 hours after trial product administration

Population: All randomised patients in top 3 dosing tiers 3, 4 and 5 who had pharmacokinetic assessments and completed the trial without violating the protocol in a manner that was judged to affect the pharmacokinetic endpoints were included in the pharmacokinetic analysis set. Some subjects did not contribute for pharmacokinetic analysis.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=11 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=11 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=7 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=7 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time)	—	—	0.68 hours Standard Deviation 0.16	0.88 hours Standard Deviation 0.33	0.56 hours Standard Deviation 0.10	2.23 hours Standard Deviation 0.54

SECONDARY outcome

Timeframe: 0-24 hours after trial product administration

Population: All randomised patients in top 3 dosing tiers 3, 4 and 5 who had pharmacokinetic assessments and completed the trial without violating the protocol in a manner that was judged to affect the pharmacokinetic endpoints were included in the pharmacokinetic analysis set. Some subjects did not contribute for pharmacokinetic analysis.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=13 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=11 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=7 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=7 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life)	—	—	0.92 hours Standard Deviation 0.18	1.28 hours Standard Deviation 1.28	0.71 hours Standard Deviation 0.16	1.66 hours Standard Deviation 0.35

SECONDARY outcome

Timeframe: 0-24 hours after trial product administration

Population: All randomised patients in top 3 dosing tiers 3, 4 and 5 who had pharmacokinetic assessments and completed the trial without violating the protocol in a manner that was judged to affect the pharmacokinetic endpoints were included in the pharmacokinetic analysis set. Some subjects did not contribute for pharmacokinetic analysis.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=11 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=11 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=7 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=7 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance)	—	—	9365.8 mL/h Interval 6829.8 to 15065.0	11247 mL/h Interval 5315.6 to 21314.0	10409 mL/h Interval 6262.9 to 13276.0	3078.3 mL/h Interval 1636.9 to 5039.4

SECONDARY outcome

Timeframe: 0-24 hours after trial product administration

Population: All randomised patients in top 3 dosing tiers 3, 4 and 5 who had pharmacokinetic assessments and completed the trial without violating the protocol in a manner that was judged to affect the pharmacokinetic endpoints were included in the pharmacokinetic analysis set. Some subjects did not contribute for pharmacokinetic analysis.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=11 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=11 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=7 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=7 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State)	—	—	5396.9 mL/kg Interval 3319.1 to 12215.0	9597.0 mL/kg Interval 5522.7 to 18310.0	5538.7 mL/kg Interval 4210.7 to 6482.6	6696.7 mL/kg Interval 3037.3 to 10328.0

SECONDARY outcome

Timeframe: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

Immunogenicity was tested by formation of neutralising antibodies towards vatreptacog alfa and/or rFVIIa.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Immunogenicity (Inhibitor Development)	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: screening visit, pre-dose and 12 hours after dosing

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Biochemistry: ALAT (Alanine Aminotransferase) Screening	26.0 U/L Standard Deviation 18.7	32.8 U/L Standard Deviation 31.3	30.6 U/L Standard Deviation 27.1	39.3 U/L Standard Deviation 33.3	24.2 U/L Standard Deviation 17.9	30.1 U/L Standard Deviation 21.4
Biochemistry: ALAT (Alanine Aminotransferase) Pre-dose	22.7 U/L Standard Deviation 19.9	29.9 U/L Standard Deviation 23.0	32.4 U/L Standard Deviation 37.1	29.1 U/L Standard Deviation 16.4	28.1 U/L Standard Deviation 16.6	49.4 U/L Standard Deviation 73.7
Biochemistry: ALAT (Alanine Aminotransferase) 12 hours post-dose	20.1 U/L Standard Deviation 16.8	25.6 U/L Standard Deviation 19.2	21.4 U/L Standard Deviation 15.4	30.9 U/L Standard Deviation 18.2	24.5 U/L Standard Deviation 14.4	45.1 U/L Standard Deviation 66.0

SECONDARY outcome

Timeframe: screening visit, pre-dose and 12 hours after dosing

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Biochemistry: Creatinine Screening	66.9 micromol/L Standard Deviation 23.6	67.2 micromol/L Standard Deviation 13.8	63.6 micromol/L Standard Deviation 23.3	67.7 micromol/L Standard Deviation 15.7	60.0 micromol/L Standard Deviation 17.3	66.9 micromol/L Standard Deviation 16.0
Biochemistry: Creatinine Pre-dose	68.2 micromol/L Standard Deviation 23.3	70.1 micromol/L Standard Deviation 10.0	69.8 micromol/L Standard Deviation 15.3	69.1 micromol/L Standard Deviation 19.1	67.7 micromol/L Standard Deviation 10.8	71.1 micromol/L Standard Deviation 15.2
Biochemistry: Creatinine 12 hours post-dose	58.3 micromol/L Standard Deviation 23.6	63.1 micromol/L Standard Deviation 17.7	70.6 micromol/L Standard Deviation 16.8	71.9 micromol/L Standard Deviation 15.2	68.0 micromol/L Standard Deviation 10.7	70.6 micromol/L Standard Deviation 14.8

SECONDARY outcome

Timeframe: screening visit, pre-dose and 12 hours after dosing

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Haematology: Haemoglobin Screening	13.9 g/dL Standard Deviation 1.8	14.7 g/dL Standard Deviation 1.6	14.2 g/dL Standard Deviation 1.4	14.2 g/dL Standard Deviation 1.8	14.6 g/dL Standard Deviation 1.3	13.8 g/dL Standard Deviation 1.3
Haematology: Haemoglobin Pre-dose	13.8 g/dL Standard Deviation 2.3	14.6 g/dL Standard Deviation 1.7	14.4 g/dL Standard Deviation 1.2	13.9 g/dL Standard Deviation 2.1	14.8 g/dL Standard Deviation 1.3	14.1 g/dL Standard Deviation 1.3
Haematology: Haemoglobin 12 hours post-dose	13.5 g/dL Standard Deviation 2.2	13.9 g/dL Standard Deviation 1.7	13.7 g/dL Standard Deviation 1.2	13.0 g/dL Standard Deviation 2.2	14.2 g/dL Standard Deviation 0.8	13.5 g/dL Standard Deviation 1.3

SECONDARY outcome

Timeframe: screening visit, pre-dose and 12 hours after dosing

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Haematology: Red Cell Count Screening	5.0 10^12 cells/L Standard Deviation 0.5	5.4 10^12 cells/L Standard Deviation 0.9	5.3 10^12 cells/L Standard Deviation 1.0	5.1 10^12 cells/L Standard Deviation 0.4	5.7 10^12 cells/L Standard Deviation 1.2	5.3 10^12 cells/L Standard Deviation 1.0
Haematology: Red Cell Count Pre-dose	5.1 10^12 cells/L Standard Deviation 0.5	5.1 10^12 cells/L Standard Deviation 0.4	5.2 10^12 cells/L Standard Deviation 0.4	5.1 10^12 cells/L Standard Deviation 0.4	5.1 10^12 cells/L Standard Deviation 0.4	5.2 10^12 cells/L Standard Deviation 0.5
Haematology: Red Cell Count 12 hours post-dose	5.0 10^12 cells/L Standard Deviation 0.7	4.9 10^12 cells/L Standard Deviation 0.4	4.9 10^12 cells/L Standard Deviation 0.3	4.8 10^12 cells/L Standard Deviation 0.5	4.9 10^12 cells/L Standard Deviation 0.3	5.0 10^12 cells/L Standard Deviation 0.6

SECONDARY outcome

Timeframe: screening visit, pre-dose and 12 hours after dosing

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Haematology: Packed Cell Volume Screening	41.6 percentage (%) Standard Deviation 5.1	43.7 percentage (%) Standard Deviation 3.9	42.2 percentage (%) Standard Deviation 3.6	42.4 percentage (%) Standard Deviation 4.3	44.0 percentage (%) Standard Deviation 3.3	41.6 percentage (%) Standard Deviation 3.8
Haematology: Packed Cell Volume Pre-dose	41.3 percentage (%) Standard Deviation 6.1	43.1 percentage (%) Standard Deviation 4.0	42.6 percentage (%) Standard Deviation 3.2	42.5 percentage (%) Standard Deviation 6.3	44.6 percentage (%) Standard Deviation 4.6	42.3 percentage (%) Standard Deviation 3.5
Haematology: Packed Cell Volume 12 hours post-dose	40.6 percentage (%) Standard Deviation 6.0	40.9 percentage (%) Standard Deviation 4.0	40.6 percentage (%) Standard Deviation 2.9	39.9 percentage (%) Standard Deviation 6.8	42.2 percentage (%) Standard Deviation 2.9	40.4 percentage (%) Standard Deviation 3.8

SECONDARY outcome

Timeframe: screening visit, pre-dose and 12 hours after dosing

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Haematology: White Cell Count Screening	6.7 10^9 cells/L Standard Deviation 1.9	6.3 10^9 cells/L Standard Deviation 2.5	7.2 10^9 cells/L Standard Deviation 2.4	6.9 10^9 cells/L Standard Deviation 2.7	6.6 10^9 cells/L Standard Deviation 1.5	5.8 10^9 cells/L Standard Deviation 1.8
Haematology: White Cell Count Pre-dose	7.6 10^9 cells/L Standard Deviation 2.3	7.3 10^9 cells/L Standard Deviation 2.6	7.8 10^9 cells/L Standard Deviation 1.9	7.1 10^9 cells/L Standard Deviation 2.2	7.1 10^9 cells/L Standard Deviation 2.3	6.5 10^9 cells/L Standard Deviation 2.1
Haematology: White Cell Count 12 hours post-dose	7.7 10^9 cells/L Standard Deviation 3.4	7.2 10^9 cells/L Standard Deviation 2.1	8.2 10^9 cells/L Standard Deviation 2.0	7.3 10^9 cells/L Standard Deviation 2.6	6.8 10^9 cells/L Standard Deviation 1.4	7.1 10^9 cells/L Standard Deviation 2.5

SECONDARY outcome

Timeframe: screening visit, pre-dose and 12 hours after dosing

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.

Outcome measures

Measure	Vatreptacog Alfa 5 mcg/kg n=16 Participants Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 Participants Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 Participants Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 Participants Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 Participants Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=17 Participants Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Haematology: Platelet Count 12 hours post-dose	242.7 10^9 cells/L Standard Deviation 83.7	244.8 10^9 cells/L Standard Deviation 57.4	255.8 10^9 cells/L Standard Deviation 61.9	287.0 10^9 cells/L Standard Deviation 94.8	266.8 10^9 cells/L Standard Deviation 53.1	260.7 10^9 cells/L Standard Deviation 69.4
Haematology: Platelet Count Screening	259.8 10^9 cells/L Standard Deviation 96.2	253.8 10^9 cells/L Standard Deviation 82.9	250.8 10^9 cells/L Standard Deviation 61.2	276.1 10^9 cells/L Standard Deviation 75.5	272.5 10^9 cells/L Standard Deviation 73.2	259.0 10^9 cells/L Standard Deviation 86.1
Haematology: Platelet Count Pre-dose	253.5 10^9 cells/L Standard Deviation 90.5	248.6 10^9 cells/L Standard Deviation 65.2	252.7 10^9 cells/L Standard Deviation 50.8	278.8 10^9 cells/L Standard Deviation 78.0	278.1 10^9 cells/L Standard Deviation 59.0	271.1 10^9 cells/L Standard Deviation 82.4

Adverse Events

Vatreptacog Alfa 5 mcg/kg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Vatreptacog Alfa 10 mcg/kg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Vatreptacog Alfa 20 mcg/kg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Vatreptacog Alfa 40 mcg/kg

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Vatreptacog Alfa 80 mcg/kg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

rFVIIa 90 mcg/kg

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vatreptacog Alfa 5 mcg/kg n=16 participants at risk Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 participants at risk Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 participants at risk Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 participants at risk Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 participants at risk Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=19 participants at risk Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Gastrointestinal disorders Colonic polyp	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Gastrointestinal disorders Dyspepsia	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
General disorders Device dislocation	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Hepatobiliary disorders Cholecystitis	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Infections and infestations Arthritis bacterial	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Musculoskeletal and connective tissue disorders Compartment syndrome	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Musculoskeletal and connective tissue disorders Muscle atrophy	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Renal and urinary disorders Haematuria	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Surgical and medical procedures Removal of foreign body from joint	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Vascular disorders Aneurysm	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Vascular disorders Thrombophlebitis superficial	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.

Other adverse events

Measure	Vatreptacog Alfa 5 mcg/kg n=16 participants at risk Subjects received vatreptacog alfa 5 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 10 mcg/kg n=19 participants at risk Subjects received vatreptacog alfa 10 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 20 mcg/kg n=16 participants at risk Subjects received vatreptacog alfa 20 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 40 mcg/kg n=16 participants at risk Subjects received vatreptacog alfa 40 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	Vatreptacog Alfa 80 mcg/kg n=10 participants at risk Subjects received vatreptacog alfa 80 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to one qualifying bleeding episode per vatreptacog alfa arm.	rFVIIa 90 mcg/kg n=19 participants at risk Subjects received rFVIIa standard dose regimen 90 mcg/kg intravenously every 3 hours (+ 30 minutes) maximum of 3 times until bleeding was controlled. A subject could contribute with up to 5 qualifying bleeding episode per to the rFVIIa arm, corresponding to number of dose escalation cohorts.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Gastrointestinal disorders Diarrhoea	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	10.5% 2/19 • Number of events 2 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Gastrointestinal disorders Nausea	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Gastrointestinal disorders Teeth brittle	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
General disorders Discomfort	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
General disorders Infusion site extravasation	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
General disorders Injection site haematoma	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
General disorders Injection site haemorrhage	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
General disorders Pyrexia	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Infections and infestations Nasopharyngitis	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Injury, poisoning and procedural complications Incorrect dose administered	18.8% 3/16 • Number of events 3 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Injury, poisoning and procedural complications Traumatic haemorrhage	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Investigations Alanine aminotransferase increased	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Musculoskeletal and connective tissue disorders Ligament disorder	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Nervous system disorders Dizziness	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Skin and subcutaneous tissue disorders Pruritus allergic	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Vascular disorders Hypotension	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	6.2% 1/16 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.
Vascular disorders Thrombophlebitis	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/19 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/16 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	0.00% 0/10 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.	5.3% 1/19 • Number of events 1 • Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. Safety analysis set includes all subjects who received at least one dose of the investigational product.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee The information obtained during the conduct of this trial is considered confidential and can be used by Novo Nordisk for regulatory purposes and for the general development of the trial product. The information obtained during this trial may be made available to other physicians who are conducting other clinical trials with the trial product, if deemed necessary by Novo Nordisk.
• Publication restrictions are in place

Restriction type: OTHER