Pharmacokinetic Comparison of Advate rAHF-PFM With Recombinate rAHF in Patients With Severe Hemophilia A
- Conditions
- Hemophilia A
- Interventions
- Drug: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM)Drug: Recombinant Factor VIII (rAHF)
- Registration Number
- NCT00666406
- Lead Sponsor
- Baxalta now part of Shire
- 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%).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 9
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 1 Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Advate rAHF-PFM 2 Recombinant Factor VIII (rAHF) Recombinate rAHF
- Primary Outcome Measures
Name Time Method 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 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.
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. 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.
- Secondary Outcome Measures
Name Time Method 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.
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.
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.
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.
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.
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.
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.
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).
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
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
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). 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.
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.
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.
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.
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).
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
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.
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).
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
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
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. 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.
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). 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
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.
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
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.
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).