Clinical trial NCT00666406: Pharmacokinetic Comparison of Advate rAHF-PFM With Recombinate rAHF in Patients With Severe Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-04-24
Enrollment: 9
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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%).


Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
Secondary outcomes:
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Systemic Clearance (Cl). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Systemic Clearance (Cl). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Systemic Clearance (Cl). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Systemic Clearance (Cl). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Maximum Plasma Concentration (C-max). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Maximum Plasma Concentration (C-max). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Maximum Plasma Concentration (C-max). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Maximum Plasma Concentration (C-max). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Terminal Half-life. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Terminal Half-life. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Terminal Half-life. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Terminal Half-life. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Incremental Recovery. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Incremental Recovery. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Incremental Recovery. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Incremental Recovery. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Mean Residence Time (MRT). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Mean Residence Time (MRT). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Mean Residence Time (MRT). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Mean Residence Time (MRT). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Time to Reach the Maximum Plasma Concentration (Tmax). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Time to Reach the Maximum Plasma Concentration (Tmax). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Time to Reach the Maximum Plasma Concentration (Tmax). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Volume of Distribution at Steady State (Vss). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Volume of Distribution at Steady State (Vss). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: 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)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
measure: Volume of Distribution at Steady State (Vss). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)
timeFrame: 0-30 minutes before infusion up to 48 hours post-infusion
Other outcomes:
Locations:
city: Bonn
country: Germany
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: