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Pharmacokinetic Comparison of Advate rAHF-PFM With Recombinate rAHF in Patients With Severe Hemophilia A

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00666406
First Posted: April 24, 2008
Last Update Posted: July 21, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Shire
  Purpose
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%).

Condition Intervention Phase
Hemophilia A Drug: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Drug: Recombinant Factor VIII (rAHF) Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetic Comparison of Advate rAHF-PFM With Recombinate rAHF in Patients With Severe Hemophilia A: a Phase IV, Prospective, Randomized, Controlled, Cross-over, Single Center Study

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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:
  • 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) [ Time Frame: 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


  • 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 0-30 minutes before infusion up to 48 hours post-infusion ]
    Increase in factor VIII concentration from pre- to post-infusion

  • Incremental Recovery. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 0-30 minutes before infusion up to 48 hours post-infusion ]
    Computed as weight-adjusted CL * Mean Residence Time


Enrollment: 9
Study Start Date: March 2008
Study Completion Date: September 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Advate rAHF-PFM
Drug: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM)
Infusion of 50 +/- 5 IU/kg bodyweight
Other Names:
  • Advate rAHF-PFM
  • Recombinant Protein-Free Factor VIII (rAHF-PFM)
Active Comparator: 2
Recombinate rAHF
Drug: Recombinant Factor VIII (rAHF)
Infusion of 50 +/- 5 IU/kg bodyweight
Other Names:
  • Recombinate rAHF
  • Antihemophilic Factor (Recombinant)

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00666406


Locations
Germany
Bonn, Germany, 53127
Sponsors and Collaborators
Shire
Investigators
Study Director: Brigitt Abbühl, MD Baxter Healthcare Corporation
  More Information

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00666406     History of Changes
Other Study ID Numbers: 060601
First Submitted: April 22, 2008
First Posted: April 24, 2008
Results First Submitted: February 13, 2013
Results First Posted: March 26, 2013
Last Update Posted: July 21, 2015
Last Verified: February 2013

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants