Hemophilia A
Conditions
Brief summary
The purpose of this study is to compare the pharmacokinetic parameters and safety of Advate rAHF-PFM versus Recombinate rAHF in well described previously treated patients with severe hemophilia A (factor VIII level \< 1%).
Interventions
DRUGAntihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM)
Infusion of 50 +/- 5 IU/kg bodyweight
DRUGRecombinant Factor VIII (rAHF)
Infusion of 50 +/- 5 IU/kg bodyweight
Sponsors
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent obtained from participant or legally authorized representative * 15-60 years old * Factor VIII level \< 1% as documented by previously measured factor VIII and genotyping * Previously treated with factor VIII concentrate(s) for a minimum of at least 150 exposure days (as documented by the study site investigator) prior to study entry * Observed decrease of efficacy by subject and/or treating physician after being switched from Recombinate rAHF to Advate rAHF-PFM
Exclusion criteria
* The participant has a detectable factor VIII inhibitor at screening, with a titer \>= 0.4 Bethesda Unit (BU) (Nijmegen modification of the Bethesda Assay) measured at the local and the central laboratory * The participant has a known hypersensitivity to mouse or hamster proteins * The participant is participating in another investigational drug study within 30 days prior to screening * The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. One-Stage Activated Partial Thromboplastin Time (aPTT) -Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Clearance (Cl). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve. |
| Systemic Clearance (Cl). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve. |
| Systemic Clearance (Cl). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve. |
| Systemic Clearance (Cl). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve. |
| Maximum Plasma Concentration (C-max). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate. |
| Maximum Plasma Concentration (C-max). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate. |
| Maximum Plasma Concentration (C-max). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate. |
| Maximum Plasma Concentration (C-max). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate. |
| Terminal Half-life. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations (9 to 48 hours). |
| Terminal Half-life. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations. |
| Terminal Half-life. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations. |
| Terminal Half-life. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations. |
| Incremental Recovery. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | Increase in factor VIII concentration from pre- to post-infusion. |
| Incremental Recovery. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed from the terminal or disposition rate constant obtained from log\_e -linear fitting using the least squares deviation to the last five quantifiable concentrations. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. FVIII activity measurement |
| Incremental Recovery. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Increase in factor VIII concentration from pre- to post-infusion |
| Mean Residence Time (MRT). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve. |
| Mean Residence Time (MRT). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve. |
| Mean Residence Time (MRT). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve. |
| Mean Residence Time (MRT). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve. |
| Time to Reach the Maximum Plasma Concentration (Tmax). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax). |
| Time to Reach the Maximum Plasma Concentration (Tmax). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax). |
| Time to Reach the Maximum Plasma Concentration (Tmax). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax). |
| Time to Reach the Maximum Plasma Concentration (Tmax). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax). |
| Volume of Distribution at Steady State (Vss). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed as weight-adjusted Clearance \* Mean Residence Time |
| Volume of Distribution at Steady State (Vss). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed as weight-adjusted Clearance (CL) \* Mean Residence Time |
| Volume of Distribution at Steady State (Vss). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed as weight-adjusted CL \* Mean Residence Time |
| Volume of Distribution at Steady State (Vss). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Computed as weight-adjusted CL \* Mean Residence Time |
| Incremental Recovery. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | Increase in factor VIII concentration from pre- to post-infusion |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0-30 minutes before infusion up to 48 hours post-infusion | AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. |
Countries
Germany
Participant flow
Recruitment details
9 unique participants enrolled and treated at a single study site in Germany
Pre-assignment details
Participants required a factor VIII (FVIII) washout period ≥48 hours before receiving any pharmacokinetic (PK) infusions and could not be actively bleeding at the time of the infusion.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Includes groups randomized to receive Advate rAHF-PFM and Recombinate rAHF first. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 14.9 |
| Region of Enrollment Germany | 9 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1180 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1358 IU*h/dL |
90% CI: [1.043, 1.243]
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1505 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1664 IU*h/dL |
90% CI: [0.972, 1.179]
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 833 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 901 IU*h/dL |
90% CI: [0.866, 1.297]
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. One-Stage Activated Partial Thromboplastin Time (aPTT) -Based Assay Performed at Central Laboratory (Medical University Vienna)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. One-Stage Activated Partial Thromboplastin Time (aPTT) -Based Assay Performed at Central Laboratory (Medical University Vienna) | 1104 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. One-Stage Activated Partial Thromboplastin Time (aPTT) -Based Assay Performed at Central Laboratory (Medical University Vienna) | 1294 IU*h/dL |
90% CI: [1.089, 1.262]
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1282 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1452 IU*h/dL |
90% CI: [1.092, 1.18]
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1598 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1731 IU*h/dL |
90% CI: [1.007, 1.186]
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 874 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 926 IU*h/dL |
90% CI: [0.857, 1.253]
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. FVIII activity measurement
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 1190 IU*h/dL |
| Recombinate rAHF | Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 1393 IU*h/dL |
90% CI: [1.099, 1.247]
Secondary
Incremental Recovery. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Computed from the terminal or disposition rate constant obtained from log\_e -linear fitting using the least squares deviation to the last five quantifiable concentrations.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Incremental Recovery. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 2.04 (IU/dL)/(IU/kg) |
| Recombinate rAHF | Incremental Recovery. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 2.33 (IU/dL)/(IU/kg) |
90% CI: [1.038, 1.279]
Secondary
Incremental Recovery. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Increase in factor VIII concentration from pre- to post-infusion
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Incremental Recovery. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1.94 (IU/dL)/(IU/kg) |
| Recombinate rAHF | Incremental Recovery. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 2.19 (IU/dL)/(IU/kg) |
90% CI: [1.012, 1.27]
Secondary
Incremental Recovery. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Increase in factor VIII concentration from pre- to post-infusion
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Incremental Recovery. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1.53 (IU/dL)/(IU/kg) |
| Recombinate rAHF | Incremental Recovery. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 1.84 (IU/dL)/(IU/kg) |
90% CI: [1.027, 1.362]
Secondary
Incremental Recovery. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
Increase in factor VIII concentration from pre- to post-infusion.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Incremental Recovery. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 1.81 (IU/dL)/(IU/kg) |
| Recombinate rAHF | Incremental Recovery. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 2.11 (IU/dL)/(IU/kg) |
90% CI: [1.106, 1.254]
Secondary
Maximum Plasma Concentration (C-max). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Maximum Plasma Concentration (C-max). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 104 IU/dL |
| Recombinate rAHF | Maximum Plasma Concentration (C-max). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 119 IU/dL |
90% CI: [1.039, 1.277]
Secondary
Maximum Plasma Concentration (C-max). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Maximum Plasma Concentration (C-max). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 100 IU/dL |
| Recombinate rAHF | Maximum Plasma Concentration (C-max). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 112 IU/dL |
90% CI: [1.01, 1.27]
Secondary
Maximum Plasma Concentration (C-max). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Maximum Plasma Concentration (C-max). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 78 IU/dL |
| Recombinate rAHF | Maximum Plasma Concentration (C-max). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 94 IU/dL |
90% CI: [1.029, 1.359]
Secondary
Maximum Plasma Concentration (C-max). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Maximum Plasma Concentration (C-max). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 93 IU/dL |
| Recombinate rAHF | Maximum Plasma Concentration (C-max). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 108 IU/dL |
90% CI: [1.104, 1.256]
Secondary
Mean Residence Time (MRT). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Mean Residence Time (MRT). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 15.1 Hours |
| Recombinate rAHF | Mean Residence Time (MRT). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 14.2 Hours |
90% CI: [0.849, 1.112]
Secondary
Mean Residence Time (MRT). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Mean Residence Time (MRT). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 17.3 Hours |
| Recombinate rAHF | Mean Residence Time (MRT). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 16.9 Hours |
90% CI: [0.894, 1.111]
Secondary
Mean Residence Time (MRT). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Mean Residence Time (MRT). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 12.5 Hours |
| Recombinate rAHF | Mean Residence Time (MRT). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 12.8 Hours |
90% CI: [0.938, 1.109]
Secondary
Mean Residence Time (MRT). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Mean Residence Time (MRT). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 14.1 Hours |
| Recombinate rAHF | Mean Residence Time (MRT). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 14.4 Hours |
90% CI: [0.964, 1.056]
Secondary
Systemic Clearance (Cl). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Systemic Clearance (Cl). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 4.00 mL/h/kg |
| Recombinate rAHF | Systemic Clearance (Cl). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 3.53 mL/h/kg |
90% CI: [0.847, 0.916]
Secondary
Systemic Clearance (Cl). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Systemic Clearance (Cl). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 3.21 mL/h/kg |
| Recombinate rAHF | Systemic Clearance (Cl). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 2.96 mL/h/kg |
90% CI: [0.841, 0.995]
Secondary
Systemic Clearance (Cl). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Systemic Clearance (Cl). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 5.87 mL/h/kg |
| Recombinate rAHF | Systemic Clearance (Cl). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 5.53 mL/h/kg |
90% CI: [0.799, 1.164]
Secondary
Systemic Clearance (Cl). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Systemic Clearance (Cl). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 4.31 mL/h/kg |
| Recombinate rAHF | Systemic Clearance (Cl). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 3.68 mL/h/kg |
90% CI: [0.798, 0.913]
Secondary
Terminal Half-life. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Terminal Half-life. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 11.7 hours |
| Recombinate rAHF | Terminal Half-life. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 10.8 hours |
90% CI: [0.843, 1.102]
Secondary
Terminal Half-life. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Terminal Half-life. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 12.4 hours |
| Recombinate rAHF | Terminal Half-life. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 12.1 hours |
90% CI: [0.901, 1.144]
Secondary
Terminal Half-life. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations.
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Terminal Half-life. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 9.5 hours |
| Recombinate rAHF | Terminal Half-life. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 9.9 hours |
90% CI: [0.926, 1.163]
Secondary
Terminal Half-life. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations (9 to 48 hours).
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Terminal Half-life. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 10.7 hours |
| Recombinate rAHF | Terminal Half-life. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 10.9 hours |
90% CI: [0.969, 1.05]
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Time to Reach the Maximum Plasma Concentration (Tmax). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0.31 Hours |
| Recombinate rAHF | Time to Reach the Maximum Plasma Concentration (Tmax). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0.42 Hours |
90% CI: [0.841, 2.02]
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Time to Reach the Maximum Plasma Concentration (Tmax). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0.38 Hours |
| Recombinate rAHF | Time to Reach the Maximum Plasma Concentration (Tmax). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0.51 Hours |
90% CI: [0.442, 2.539]
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Time to Reach the Maximum Plasma Concentration (Tmax). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0.45 Hours |
| Recombinate rAHF | Time to Reach the Maximum Plasma Concentration (Tmax). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 0.31 Hours |
90% CI: [0.304, 1.728]
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Time to Reach the Maximum Plasma Concentration (Tmax). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0.25 Hours |
| Recombinate rAHF | Time to Reach the Maximum Plasma Concentration (Tmax). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 0.25 Hours |
90% CI: [1, 1]
Secondary
Volume of Distribution at Steady State (Vss). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Computed as weight-adjusted Clearance (CL) \* Mean Residence Time
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Volume of Distribution at Steady State (Vss). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 60.4 mL/kg |
| Recombinate rAHF | Volume of Distribution at Steady State (Vss). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 50.2 mL/kg |
90% CI: [0.73, 1.002]
Secondary
Volume of Distribution at Steady State (Vss). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Computed as weight-adjusted CL \* Mean Residence Time
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Volume of Distribution at Steady State (Vss). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 55.6 mL/kg |
| Recombinate rAHF | Volume of Distribution at Steady State (Vss). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 50.0 mL/kg |
90% CI: [0.8, 1.039]
Secondary
Volume of Distribution at Steady State (Vss). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
Computed as weight-adjusted CL \* Mean Residence Time
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Volume of Distribution at Steady State (Vss). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 73.2 mL/kg |
| Recombinate rAHF | Volume of Distribution at Steady State (Vss). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site) | 70.9 mL/kg |
90% CI: [0.788, 1.228]
Secondary
Volume of Distribution at Steady State (Vss). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
Computed as weight-adjusted Clearance \* Mean Residence Time
Time frame: 0-30 minutes before infusion up to 48 hours post-infusion
Population: All enrolled participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Advate rAHF-PFM | Volume of Distribution at Steady State (Vss). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 60.8 mL/kg |
| Recombinate rAHF | Volume of Distribution at Steady State (Vss). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) | 52.9 mL/kg |
90% CI: [0.807, 0.92]