Trial Outcomes & Findings for BAX 826 Dose-Escalation Safety Study (NCT NCT02716194)

NCT ID: NCT02716194

Last Updated: 2021-05-25

Results Overview

Serious Adverse Events and non-serious Adverse Events the occurred after infusion with BAX 826.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

Up to 6 weeks ± 4 days post infusion with BAX826.

Results posted on

2021-05-25

Participant Flow

The study was conducted at 20 study sites in the EU and Russia. 44 participants signed informed consent. Of these, 4 participants were not treated (2 screen failures and 2 participants withdrew from study prior to receiving any dosing).

44 participants signed informed consent. Of these, 4 participants were not treated (2 screen failures and 2 participants withdrew from study prior to receiving any dosing).

Participant milestones

Participant milestones
Measure	Cohort 1 - Low Dose Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Period 1 - ADVATE STARTED	11	16	13
Period 1 - ADVATE COMPLETED	10	15	13
Period 1 - ADVATE NOT COMPLETED	1	1	0
Period 2 - BAX 826 STARTED	10	15	13
Period 2 - BAX 826 COMPLETED	10	15	13
Period 2 - BAX 826 NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 - Low Dose Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Period 1 - ADVATE Withdrawal by Subject	1	1	0

Baseline Characteristics

BAX 826 Dose-Escalation Safety Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Total n=40 Participants Total of all reporting groups
Age, Continuous	34.0 Years n=5 Participants	33.0 Years n=7 Participants	36.0 Years n=5 Participants	34.0 Years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	16 Participants n=7 Participants	13 Participants n=5 Participants	40 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	10 Participants n=5 Participants	16 Participants n=7 Participants	13 Participants n=5 Participants	39 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 6 weeks ± 4 days post infusion with BAX826.

Population: Participants in Cohort 1, 2 and 3 in Period 2 (receiving BAX 826) are included.

Serious Adverse Events and non-serious Adverse Events the occurred after infusion with BAX 826.

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=10 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=15 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any treatment related non-serious AE	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any moderate or severe non-serious AE	8 Adverse Events	3 Adverse Events	4 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any AE	20 Adverse Events	12 Adverse Events	15 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any AE with outcome = Death	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any serious AE	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any treatment related serious AE	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any moderate or severe serious AE	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any non-serious AE	20 Adverse Events	12 Adverse Events	15 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any systemic AE	1 Adverse Events	0 Adverse Events	4 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any treatment related systemic AE	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any moderate or severe systemic AE	0 Adverse Events	0 Adverse Events	1 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any local/non-systemic AE	19 Adverse Events	12 Adverse Events	11 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any treatment related local/non-systemic AE	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any moderate or severe local/non-systemic AE	8 Adverse Events	3 Adverse Events	3 Adverse Events	—	—	—
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 Any AE leading to study treatment withdrawal	0 Adverse Events	0 Adverse Events	0 Adverse Events	—	—	—

PRIMARY outcome

Timeframe: Screening (Day -30 to -2); Advate Administration (Study Day 1) pre & postdose, and Day 4; Advate washout 96 hours to 4 weeks; BAX826 Administration Day 1 pre & postdose, Post BAX826 Day 4, 8, 14, and 23; and study termination visit, week 6 ± 4 days

Clinically significant results after treatment with investigational product that constitute an AE are counted. Vital signs include body temperature, respiratory rate, pulse rate, and blood pressure. Clinical laboratory results include: Hematology (hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (i.e. basophils, eosinophils, lymphocytes, monocytes and neutrophils), international normalized ratio (INR), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count. Clinical Chemistry: sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), blood urea nitrogen (BUN), creatinine, glucose. Lipid panel: cholesterol, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments) Clinically significant vital signs	0 Participants	0 Participants	0 Participants	—	—	—
Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments) Clinically sign. laboratory results after Advate	0 Participants	0 Participants	1 Participants	—	—	—
Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments) Clinically sign. laboratory results after BAX826	0 Participants	0 Participants	3 Participants	—	—	—

PRIMARY outcome

Timeframe: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days

Population: The immunogenicity analysis was performed on the participants of the safety population (participants who received at least one administration of BAX 826 or ADVATE) who have a predose and at least one postdose result.

Inhibition of FVIII activity by antibodies binding to FVIII were measured using the Nijmegen modification of the Bethesda inhibitor assay.

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=10 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=14 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Immunogenicity: Inhibitory Antibodies to Factor VIII (FVIII)	0 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

Binding antibodies to PSA FVIII (ie BAX 826) IgG and IgM

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=10 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=14 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 n=10 Participants After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 n=15 Participants After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 n=13 Participants After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826) IgG: At least 1 positive result (includ.predose)	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826) IgG: Predose negative / Postdose positive	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826) IgM: At least 1 positive result (includ.predose)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826) IgM: Predose negative / Postdose positive	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Binding antibodies to FVIII IgG and IgM

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=14 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 n=10 Participants After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 n=15 Participants After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 n=13 Participants After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Immunogenicity: Binding Antibodies to Factor VIII (FVIII) IgG: At least 1 positive result (includ.predose)	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Immunogenicity: Binding Antibodies to Factor VIII (FVIII) IgG: Predose negative / Postdose positive	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Immunogenicity: Binding Antibodies to Factor VIII (FVIII) IgM: At least 1 positive result (includ.predose)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Immunogenicity: Binding Antibodies to Factor VIII (FVIII) IgM: Predose negative / Postdose positive	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Binding antibodies to PSA (IgG and IgM)

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=14 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 n=10 Participants After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 n=15 Participants After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 n=13 Participants After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies IgG: At least 1 positive result (includ.predose)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies IgG: Predose negative / Postdose positive	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies IgM: At least 1 positive result (includ.predose)	0 Participants	1 Participants	3 Participants	0 Participants	1 Participants	3 Participants
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies IgM: Predose negative / Postdose positive	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Binding antibodies to CHO

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=10 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=15 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Immunogenicity: Anti-Chinese Hamster Ovary (Anti-CHO) Antibodies	0 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

Binding antibodies HAMA (IgG)

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=10 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=15 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=13 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Immunogenicity: Human Anti-murine Antibodies (HAMA)	0 Participants	0 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.

Population: In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2).

Area under the FVIII activity-time curve from zero extrapolated to infinity, calculated by linear-up/log-down trapezoidal method and extrapolated to infinity, calculated as AUC last + C last / lambda z, where Clast is the estimated concentration at the last quantifiable time point

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) Period 2 (BAX 826) - One Stage Clotting Assay	1127 IU*h/dL Geometric Coefficient of Variation 73.1	2363 IU*h/dL Geometric Coefficient of Variation 24.3	2578 IU*h/dL Geometric Coefficient of Variation 55.0	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) Period 1 (ADVATE) - Chromogenic Assay	818.9 IU*h/dL Geometric Coefficient of Variation 38.6	1747 IU*h/dL Geometric Coefficient of Variation 31.0	2693 IU*h/dL Geometric Coefficient of Variation 34.9	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) Period 1 (ADVATE) - One Stage Clotting Assay	901.3 IU*h/dL Geometric Coefficient of Variation 43.3	1771 IU*h/dL Geometric Coefficient of Variation 30.9	2496 IU*h/dL Geometric Coefficient of Variation 39.3	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) Period 2 (BAX 826) - Chromogenic Assay	1234 IU*h/dL Geometric Coefficient of Variation 67.4	2742 IU*h/dL Geometric Coefficient of Variation 36.4	3791 IU*h/dL Geometric Coefficient of Variation 55.9	—	—	—

SECONDARY outcome

Terminal elimination phase half-life, calculated by (ln2)/lambda z, where lambda z is the terminal rate constant, determined by linear regression of the terminal points of the log-linear FVIII activity-time curve.

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Terminal Half-life (t1/2) Period 2 (BAX 826) - One Stage Clotting Assay	16.18 hours Geometric Coefficient of Variation 41.3	16.90 hours Geometric Coefficient of Variation 21.0	16.22 hours Geometric Coefficient of Variation 28.1	—	—	—
Pharmacokinetics: Terminal Half-life (t1/2) Period 1 (ADVATE) - Chromogenic Assay	11.23 hours Geometric Coefficient of Variation 35.4	11.21 hours Geometric Coefficient of Variation 35.7	12.11 hours Geometric Coefficient of Variation 28.5	—	—	—
Pharmacokinetics: Terminal Half-life (t1/2) Period 1 (ADVATE) - One Stage Clotting Assay	10.57 hours Geometric Coefficient of Variation 39.1	11.30 hours Geometric Coefficient of Variation 29.6	9.948 hours Geometric Coefficient of Variation 34.8	—	—	—
Pharmacokinetics: Terminal Half-life (t1/2) Period 2 (BAX826) - Chromogenic Assay	16.04 hours Geometric Coefficient of Variation 35.6	15.21 hours Geometric Coefficient of Variation 20.2	16.72 hours Geometric Coefficient of Variation 28.2	—	—	—

SECONDARY outcome

Mean residence time, calculated as (AUMC 0-∞ / AUC 0-∞) - TI / 2, where TI is the time duration of infusion

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Mean Residence Time (MRT) Period 1 (ADVATE) - One Stage Clotting Assay	15.55 hours Geometric Coefficient of Variation 39.9	16.30 hours Geometric Coefficient of Variation 30.5	14.00 hours Geometric Coefficient of Variation 29.7	—	—	—
Pharmacokinetics: Mean Residence Time (MRT) Period 2 (BAX 826) - One Stage Clotting Assay	26.96 hours Geometric Coefficient of Variation 43.4	28.90 hours Geometric Coefficient of Variation 17.4	24.33 hours Geometric Coefficient of Variation 27.8	—	—	—
Pharmacokinetics: Mean Residence Time (MRT) Period 1 (ADVATE) - Chromogenic Assay	15.23 hours Geometric Coefficient of Variation 36.1	14.56 hours Geometric Coefficient of Variation 29.5	15.36 hours Geometric Coefficient of Variation 29.1	—	—	—
Pharmacokinetics: Mean Residence Time (MRT) Period 2 (BAX826) - Chromogenic Assay	24.26 hours Geometric Coefficient of Variation 34.1	22.83 hours Geometric Coefficient of Variation 20.3	24.10 hours Geometric Coefficient of Variation 28.2	—	—	—

SECONDARY outcome

Systemic body clearance of drug from plasma, calculated by dose (IU/kg)/AUC0-∞

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Total Body Clearance (CL) Period 1 (ADVATE) - One Stage Clotting Assay	0.02803 dL/kg*h Geometric Coefficient of Variation 47.0	0.02831 dL/kg*h Geometric Coefficient of Variation 31.4	0.02989 dL/kg*h Geometric Coefficient of Variation 39.3	—	—	—
Pharmacokinetics: Total Body Clearance (CL) Period 2 (BAX 826) - One Stage Clotting Assay	0.02213 dL/kg*h Geometric Coefficient of Variation 74.8	0.02161 dL/kg*h Geometric Coefficient of Variation 25.4	0.02950 dL/kg*h Geometric Coefficient of Variation 55.8	—	—	—
Pharmacokinetics: Total Body Clearance (CL) Period 1 (ADVATE) - Chromogenic Assay	0.03085 dL/kg*h Geometric Coefficient of Variation 42.2	0.02871 dL/kg*h Geometric Coefficient of Variation 31.5	0.02771 dL/kg*h Geometric Coefficient of Variation 33.7	—	—	—
Pharmacokinetics: Total Body Clearance (CL) Period 2 (BAX 826) - Chromogenic Assay	0.02022 dL/kg*h Geometric Coefficient of Variation 69.4	0.01862 dL/kg*h Geometric Coefficient of Variation 37.4	0.02006 dL/kg*h Geometric Coefficient of Variation 57.0	—	—	—

SECONDARY outcome

Population: In period 1 (ADVATE) the number of participants is 11,15,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (9 participants were excluded from the PK analysis for period 2).

Incremental recovery (IR) at Cmax, calculated as IR = (Cmax - Cpreinfusion) / Dose (IU/kg)

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=15 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Incremental Recovery (IR) Period 1 (ADVATE) - One Stage Clotting Assay	2.506 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 18.1	2.594 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 17.0	3.059 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 25.3	—	—	—
Pharmacokinetics: Incremental Recovery (IR) Period 2 (BAX 826) - One Stage Clotting Assay	1.544 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 27.5	1.560 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 22.0	1.641 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 41.2	—	—	—
Pharmacokinetics: Incremental Recovery (IR) Period 1 (ADVATE) - Chromogenic Assay	2.850 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 14.6	3.194 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 13.0	3.467 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 20.4	—	—	—
Pharmacokinetics: Incremental Recovery (IR) Period 2 (BAX826) - Chromogenic Assay	2.391 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 26.4	2.781 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 35.2	2.512 (IU/dL)/(IU/kg) Geometric Coefficient of Variation 26.2	—	—	—

SECONDARY outcome

Volume of distribution at steady state is calculated by MRT\*CL MRT=Mean residence time CL=Clearance rate

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Volume of Distribution at Steady State (Vss) Period 1 (ADVATE) - One Stage Clotting Assay	0.4359 dL/kg Geometric Coefficient of Variation 17.4	0.4615 dL/kg Geometric Coefficient of Variation 17.7	0.4183 dL/kg Geometric Coefficient of Variation 17.9	—	—	—
Pharmacokinetics: Volume of Distribution at Steady State (Vss) Period 2 (BAX 826) - One Stage Clotting Assay	0.5967 dL/kg Geometric Coefficient of Variation 29.7	0.6246 dL/kg Geometric Coefficient of Variation 24.2	0.7176 dL/kg Geometric Coefficient of Variation 28.4	—	—	—
Pharmacokinetics: Volume of Distribution at Steady State (Vss) Period 1 (ADVATE) - Chromogenic Assay	0.4700 dL/kg Geometric Coefficient of Variation 14.6	0.4181 dL/kg Geometric Coefficient of Variation 20.6	0.4256 dL/kg Geometric Coefficient of Variation 26.7	—	—	—
Pharmacokinetics: Volume of Distribution at Steady State (Vss) Period 2 (BAX 826) - Chromogenic Assay	0.4906 dL/kg Geometric Coefficient of Variation 34.6	0.4253 dL/kg Geometric Coefficient of Variation 35.5	0.4835 dL/kg Geometric Coefficient of Variation 32.4	—	—	—

SECONDARY outcome

Maximum observed FVIII activity, obtained directly from FVIII activity versus time data

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=15 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Maximum Plasma Concentration (Cmax) Period 1 (ADVATE) - One Stage Clotting Assay	63.32 IU/dL Geometric Coefficient of Variation 16.4	130.06 IU/dL Geometric Coefficient of Variation 16.4	228.24 IU/dL Geometric Coefficient of Variation 23.5	—	—	—
Pharmacokinetics: Maximum Plasma Concentration (Cmax) Period 2 (BAX 826) - One Stage Clotting Assay	38.53 IU/dL Geometric Coefficient of Variation 26.7	79.65 IU/dL Geometric Coefficient of Variation 21.4	124.78 IU/dL Geometric Coefficient of Variation 40.8	—	—	—
Pharmacokinetics: Maximum Plasma Concentration (Cmax) Period 1 (ADVATE) - Chromogenic Assay	72.00 IU/dL Geometric Coefficient of Variation 12.8	160.16 IU/dL Geometric Coefficient of Variation 12.1	258.68 IU/dL Geometric Coefficient of Variation 21.4	—	—	—
Pharmacokinetics: Maximum Plasma Concentration (Cmax) Period 2 (BAX826) - Chromogenic Assay	59.65 IU/dL Geometric Coefficient of Variation 23.8	142.00 IU/dL Geometric Coefficient of Variation 35.1	191.01 IU/dL Geometric Coefficient of Variation 25.7	—	—	—

SECONDARY outcome

Time of maximum FVIII activity is obtained directly from FVIII activity versus time data

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=15 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax) Period 2 (BAX 826) - Chromogenic Assay	0.3835 hours Interval 0.25 to 0.617	0.3165 hours Interval 0.25 to 1.067	0.3000 hours Interval 0.25 to 0.55	—	—	—
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax) Period 1 (ADVATE) - One Stage Clotting Assay	0.3000 hours Interval 0.25 to 1.033	0.3330 hours Interval 0.25 to 1.0	0.3170 hours Interval 0.25 to 3.017	—	—	—
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax) Period 2 (BAX 826) - One Stage Clotting Assay	0.3000 hours Interval 0.25 to 0.533	0.5165 hours Interval 0.283 to 1.067	0.5500 hours Interval 0.25 to 1.05	—	—	—
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax) Period 1 (ADVATE) - Chromogenic Assay	0.3000 hours Interval 0.25 to 0.633	0.3330 hours Interval 0.25 to 1.05	0.3085 hours Interval 0.25 to 1.067	—	—	—

SECONDARY outcome

Area under the FVIII activity-time curve from zero to the last quantifiable FVIII activity, calculated by linear-up/log-down trapezoidal method.

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last) Period 1 (ADVATE) - One Stage Clotting Assay	861.8 IU*h/dL Geometric Coefficient of Variation 42.5	1712 IU*h/dL Geometric Coefficient of Variation 30.9	2445 IU*h/dL Geometric Coefficient of Variation 38.3	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last) Period 2 (BAX 826) - One Stage Clotting Assay	1078 IU*h/dL Geometric Coefficient of Variation 73.7	2296 IU*h/dL Geometric Coefficient of Variation 25.8	2528 IU*h/dL Geometric Coefficient of Variation 55.9	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last) Period 1 (ADVATE) - Chromogenic Assay	785.4 IU*h/dL Geometric Coefficient of Variation 39.2	1703 IU*h/dL Geometric Coefficient of Variation 30.3	2625 IU*h/dL Geometric Coefficient of Variation 34.6	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last) Period 2 (BAX 826) - Chromogenic Assay	1181 IU*h/dL Geometric Coefficient of Variation 70.8	2717 IU*h/dL Geometric Coefficient of Variation 37.4	3726 IU*h/dL Geometric Coefficient of Variation 57.2	—	—	—

SECONDARY outcome

AUC from time zero to exactly 72 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 72 hours is missing, the activity at 72 hours will be interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z).

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h) Period 1 (ADVATE) - One Stage Clotting Assay	885.9 IU*h/dL Geometric Coefficient of Variation 41.8	1736 IU*h/dL Geometric Coefficient of Variation 29.2	2463 IU*h/dL Geometric Coefficient of Variation 37.5	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h) Period 2 (BAX 826) - One Stage Clotting Assay	1041 IU*h/dL Geometric Coefficient of Variation 68.4	2168 IU*h/dL Geometric Coefficient of Variation 23.4	2421 IU*h/dL Geometric Coefficient of Variation 49.7	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h) Period 1 (ADVATE) - Chromogenic Assay	803.3 IU*h/dL Geometric Coefficient of Variation 37.3	1717 IU*h/dL Geometric Coefficient of Variation 30.0	2638 IU*h/dL Geometric Coefficient of Variation 34.0	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h) Period 2 (BAX 826) - Chromogenic Assay	1157 IU*h/dL Geometric Coefficient of Variation 63.5	2609 IU*h/dL Geometric Coefficient of Variation 35.9	3556 IU*h/dL Geometric Coefficient of Variation 51.5	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.

AUC from time zero to exactly 168 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 168 hours is missing, the activity at 168 hours was interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z). This parameter will be calculated for BAX 826 only.

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=8 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=10 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=11 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826 Period 2 (BAX 826) - One Stage Clotting Assay	1124 IU*h/dL Geometric Coefficient of Variation 72.9	2358 IU*h/dL Geometric Coefficient of Variation 24.2	2572 IU*h/dL Geometric Coefficient of Variation 54.7	—	—	—
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826 Period 2 (BAX 826) - Chromogenic Assay	1231 IU*h/dL Geometric Coefficient of Variation 67.2	2739 IU*h/dL Geometric Coefficient of Variation 36.4	3783 IU*h/dL Geometric Coefficient of Variation 55.6	—	—	—

SECONDARY outcome

The key pharmacokinetic parameters (Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from 0 to 72 hours (AUC0-72h), Maximum plasma concentration (Cmax), Terminal half-life (t1/2), Mean residence time (MRT) and Total body clearance (CL)) for ADVATE and BAX 826 have been compared.

Outcome measures

Outcome measures
Measure	Cohort 1 - Low Dose n=11 Participants Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose n=16 Participants After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose n=12 Participants After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 1 - Low Dose BAX 826 After the 4 day washout period following the infusion of 25±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 2 - Medium Dose BAX 826 After the washout period following the infusion of 50±5 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.	Cohort 3 - High Dose BAX 826 After the washout period following the infusion of 75±3 IU/kg ADVATE, participants received a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation.
Comparison of Key Pharmacokinetic Parameters by Cohort AUC 0-∞: One Stage Clotting Assay	116.20 Ratio of Geometric Means (%) Interval 83.53 to 161.64	122.53 Ratio of Geometric Means (%) Interval 108.19 to 138.78	100.79 Ratio of Geometric Means (%) Interval 78.64 to 129.19	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort AUC 0-∞: Chromogenic Assay	141.10 Ratio of Geometric Means (%) Interval 98.78 to 201.55	155.57 Ratio of Geometric Means (%) Interval 128.11 to 188.92	138.99 Ratio of Geometric Means (%) Interval 106.1 to 182.08	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort AUC 0-72: One Stage Clotting Assay	109.28 Ratio of Geometric Means (%) Interval 80.72 to 147.94	115.60 Ratio of Geometric Means (%) Interval 101.89 to 131.16	96.07 Ratio of Geometric Means (%) Interval 75.91 to 121.58	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort AUC 0-72: Chromogenic Assay	135.27 Ratio of Geometric Means (%) Interval 95.99 to 190.63	150.69 Ratio of Geometric Means (%) Interval 124.2 to 182.83	133.20 Ratio of Geometric Means (%) Interval 102.95 to 172.33	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort Cmax: One Stage Clotting Assay	61.15 Ratio of Geometric Means (%) Interval 50.43 to 74.15	63.28 Ratio of Geometric Means (%) Interval 57.71 to 69.38	54.40 Ratio of Geometric Means (%) Interval 41.79 to 70.82	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort Cmax: Chromogenic Assay	82.85 Ratio of Geometric Means (%) Interval 69.48 to 98.78	89.17 Ratio of Geometric Means (%) Interval 75.31 to 105.58	73.68 Ratio of Geometric Means (%) Interval 60.37 to 89.92	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort t 1/2: One Stage Clotting Assay	142.10 Ratio of Geometric Means (%) Interval 115.18 to 175.32	147.44 Ratio of Geometric Means (%) Interval 118.53 to 183.41	159.52 Ratio of Geometric Means (%) Interval 140.28 to 181.4	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort t 1/2: Chromogenic Assay	136.97 Ratio of Geometric Means (%) Interval 118.8 to 157.91	130.84 Ratio of Geometric Means (%) Interval 108.73 to 157.45	138.28 Ratio of Geometric Means (%) Interval 124.77 to 153.26	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort MRT: One Stage Clotting Assay	157.83 Ratio of Geometric Means (%) Interval 136.9 to 181.95	165.99 Ratio of Geometric Means (%) Interval 146.9 to 187.55	171.33 Ratio of Geometric Means (%) Interval 158.83 to 184.82	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort MRT: Chromogenic Assay	148.12 Ratio of Geometric Means (%) Interval 127.7 to 171.82	151.69 Ratio of Geometric Means (%) Interval 136.33 to 168.78	156.29 Ratio of Geometric Means (%) Interval 146.73 to 166.47	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort CL: One Stage Clotting Assay	85.97 Ratio of Geometric Means (%) Interval 62.65 to 117.95	83.21 Ratio of Geometric Means (%) Interval 73.83 to 93.78	100.98 Ratio of Geometric Means (%) Interval 77.76 to 131.13	—	—	—
Comparison of Key Pharmacokinetic Parameters by Cohort CL: Chromogenic Assay	70.73 Ratio of Geometric Means (%) Interval 49.67 to 100.72	65.44 Ratio of Geometric Means (%) Interval 54.14 to 79.11	73.26 Ratio of Geometric Means (%) Interval 55.37 to 96.95	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.

Population: The PK analysis set consists of all subjects that have received at least 1 administration of ADVATE or BAX 826 and are evaluable for PK for one or both treatments.

Dose Proportionality for BAX 826 was calculated for the parameters Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-last) and Maximum plasma concentration (Cmax).